1,2,3,4-tetrahydroquinoxaline compounds having glucocorticoid receptor binding activity

ABSTRACT

A 1,2,3,4-tetrahydroquinoxaline compound represented by the following formula: 
     
       
         
         
             
             
         
       
     
     In the formula (1), R 1  represents substituents such as a halogen, an alkyl, a cycloalkyl, an aryl or a heterocyclic group; p represents 0 to 5; R 2  represents substituents such as a halogen, an alkyl, a hydroxyl or an alkoxy group; q represents 0 to 2; R 3  represents substituents such as hydrogen, an alkyl, an alkenyl, an alkylcarbonyl or an arylcarbonyl group; R 4  and R 5  independently represent substituents such as hydrogen, a halogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl or a heterocyclic group; R 6  represents substituents such as hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl or a heterocyclic group; A represents an alkylene; R 7  represents OR 8 , NR 8 R 9 , SR 8 , S(O)R 8 , S(O) 2 R 8 ; R 8  and R 9  independently represent substituents such as hydrogen, an alkyl or an alkenyl; and X represents O or S.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of application Ser. No.12/225,010 filed Sep. 11, 2008, which is the United States nationalphase application of International application PCT/JP2007/055122 filedMar. 14, 2007. The entire contents of each of application Ser. No.12/225,010 and International application PCT/JP2007/055122 are herebyincorporated by reference herein.

TECHNICAL FIELD

The present invention relates to a novel 1,2,3,4-tetrahydroquinoxalinederivative or a salt thereof, which is useful as a pharmaceutical. Thederivative has a glucocorticoid receptor binding activity and is usefulas a glucocorticoid receptor modulator having a nonsteroidal structure(a glucocorticoid receptor agonist and/or a glucocorticoid receptorantagonist).

BACKGROUND ART

A glucocorticoid receptor is a 94 kDa ligand-activated intracellulartranscriptional factor that is a member of the nuclear receptorsuperfamily. This receptor is a mediator of glucocorticoid action whicheffects the metabolism of carbohydrates, proteins, fats and the like,the suppression of the immune or inflammatory responses, the activationof the central nervous system, the regulation of the cardiovascularfunction and the basal and stress-related homeostasis and the like.

As glucocorticoid action-related diseases, metabolic disorders such asdiabetes and obesity, inflammatory diseases such as arthritis, enteritisand chronic obstructive pulmonary diseases, autoimmune diseases such asconnective tissue diseases, allergic diseases such as asthma, atopicdermatitis, allergic rhinitis and conjunctivitis, central nervous systemdiseases such as psychiatric disorders, Alzheimer's disease and drug usedisorders, cardiovascular diseases such as hypertension, hypercalcemia,hyperinsulinemia and hyperlipidemia, homeostasis-related diseasescausing an abnormality of neuro-immune-endocrine balance, glaucoma andthe like are known. (SOUGOU RINSYOU, 54(7), 1951-2076 (2005),JP-A-2002-193955.)

Therefore, a compound having a glucocorticoid receptor binding activityis considered to be useful as a preventive and/or therapeutic agent forthese diseases.

As such a compound having a glucocorticoid receptor binding activity,glucocorticoid receptor agonists synthesized in the living body such ascortisol and corticosterone, synthetic glucocorticoid receptor agonistssuch as dexamethasone, prednisone and prednisilone, non-selectiveglucocorticoid receptor antagonists such as RU486 and the like areknown. (JP-A-2002-193955)

On the other hand, compounds having a 1,2,3,4-tetrahydroquinoxalinestructure are disclosed in WO 04/099192 and JP-A-5-148243 and the like.The compounds disclosed in WO 04/099192 are protein thyrosinephosphatase inhibitors essentially having a carboxylic group. On theother hand, a large number of compounds having1,2,3,4-tetrahydroquinoxaline structure are disclosed as anti-virusagents in JP-A-5-148243. However, the present compound has not beenspecifically disclosed in any of patents.

DISCLOSURE OF THE INVENTION Problems to be Solved

It is a very interesting subject to study synthesis of a novel1,2,3,4-tetrahydroquinoxaline derivative and to find a pharmacologicalaction of the derivative.

Means of Solving Problems

The present inventors conducted studies about the synthesis of1,2,3,4-tetrahydroquinoxaline derivatives having a novel chemicalstructure, and succeeded in producing a large number of novel compounds.Further, the present inventors studied the pharmacological actions ofthe derivatives and as a result, they found that the derivatives have aglucocorticoid receptor binding activity and are useful as apharmaceutical, and thus the present invention has been completed.

That is, the present invention relates to a compound represented by thefollowing general formula (1) or a salt thereof (hereinafter referred toas “the present compound”) and a pharmaceutical composition containingthe same. Further, a preferred invention in its pharmaceutical userelates to a glucocorticoid receptor modulator, and its target diseasesare glucocorticoid receptor-related diseases, that is, metabolicdisorders such as diabetes and obesity, inflammatory diseases such asarthritis, enteritis and chronic obstructive pulmonary diseases,autoimmune diseases such as connective tissue diseases, allergicdiseases such as asthma, atopic dermatitis, allergic rhinitis andconjunctivitis, central nervous system diseases such as psychiatricdisorders, Alzheimer's disease and drug use disorders; cardiovasculardiseases such as hypertension, hypercalcemia, hyperinsulinemia andhyperlipidemia, homeostasis-related diseases causing an abnormality ofneuro-immune-endocrine balance, glaucoma and the like. A particularlypreferred invention is an invention relating to a preventive or atherapeutic agent for these diseases.

[wherein R¹ represents a halogen atom, a lower alkyl group which mayhave at least a substituent, a lower cycloalkyl group which may have atleast a substituent, an aryl group which may have at least asubstituent, a heterocyclic group which may have at least a substituent,a hydroxy group, an ester of a hydroxy group, a lower alkoxy group whichmay have at least a substituent, a lower cycloalkyloxy group which mayhave at least a substituent, an aryloxy group which may have at least asubstituent, a heterocyclic oxy group which may have at least asubstituent, a mercapto group, an ester of a mercapto group, a loweralkylthio group which may have least a substituent, a lowercycloalkylthio group which may have at least a substituent, an arylthiogroup which may have at least a substituent, a heterocyclic thio groupwhich may have at least a substituent, an amino group, a loweralkylamino group which may have at least a substituent, a lowercycloalkylamino group which may have at least a substituent, anarylamino group which may have at least a substituent, a heterocyclicamino group which may have at least a substituent, an amide of an aminogroup, an amide of a lower alkylamino group which may have at least asubstituent, an amide of a lower cycloalkylamino group which may have atleast a substituent, an amide of an arylamino group which may have atleast a substituent, an amide of heterocyclic amino group which may haveat least a substituent, a formyl group, a lower alkylcarbonyl groupwhich may have at least a substituent, a lower cycloalkylcarbonyl groupwhich may have at least a substituent, an arylcarbonyl group which mayhave at least a substituent, a heterocyclic carbonyl group which mayhave at least a substituent, a carboxy group, an ester of a carboxygroup, an amide of a carboxy group, a lower alkylsulfonyl group whichmay have at least a substituent, a lower cycloalkylsulfonyl group whichmay have at least a substituent, an arylsulfonyl group which may have atleast a substituent, a heterocyclic sulfonyl group which may have atleast a substituent, a sulfonic acid group, an ester of a sulfonic acidgroup, an amide of a sulfonic acid group, a nitro group or a cyanogroup;

p represents an integer of 0 to 5;

in the case where p is 2 to 5, each R¹ may be the same or different;

R² represents a halogen atom, a lower alkyl group which may have atleast a substituent, a hydroxy group, an ester of a hydroxy group or alower alkoxy group which may have at least a substituent;

q represents an integer of 0 to 2;

in the case where q is 2, each R² may be the same or different;

R³ represents a hydrogen atom, a lower alkyl group which may have atleast a substituent, a lower alkenyl group which may have at least asubstituent, a lower alkylcarbonyl group which may have at least asubstituent, a lower alkenylcarbonyl group which may have at least asubstituent or an arylcarbonyl group which may have at least asubstituent;

R⁴ and R⁵ may be the same or different and represent a hydrogen atom, ahalogen atom, a lower alkyl group which may have at least a substituent,a lower alkenyl group which may have at least a substituent, a loweralkynyl group which may have at least a substituent, a lower cycloalkylgroup which may have at least a substituent, an aryl group which mayhave at least a substituent or a heterocyclic group which may have atleast a substituent;

R⁴ and R⁵ may be combined together to form a 3- to 8-membered lowercycloalkane ring which may have at least a substituent;

R⁶ represents a hydrogen atom, a lower alkyl group which may have atleast a substituent, a lower alkenyl group which may have at least asubstituent, a lower alkynyl group which may have at least asubstituent, a lower cycloalkyl group which may have at least asubstituent, an aryl group which may have at least a substituent or aheterocyclic group which may have at least a substituent;

A represents a lower alkylene group which may have at least asubstituent;

R⁷ represents OR⁸, NR⁸R⁹, SR⁸, S(O)R⁸ or S(O)₂R⁸;

R⁸ and R⁹ may be the same or different and represent a hydrogen atom, alower alkyl group which may have at least a substituent, a lower alkenylgroup which may have at least a substituent, a lower alkynyl group whichmay have at least a substituent, a lower cycloalkyl group which may haveat least a substituent, an aryl group which may have at least asubstituent, a heterocyclic group which may have at least a substituent,a formyl group, a lower alkylcarbonyl group which may have at least asubstituent, a lower alkenylcarbonyl group which may have at least asubstituent, a lower alkynylcarbonyl group which may have at least asubstituent, a lower cycloalkylcarbonyl group which may have at least asubstituent, an arylcarbonyl group which may have at least asubstituent, a heterocyclic carbonyl group which may have at least asubstituent, a carboxy group, a lower alkoxycarbonyl group which mayhave at least a substituent, a lower alkenyloxycarbonyl group which mayhave at least a substituent, a lower alkynyloxycarbonyl group which mayhave at least a substituent, a lower cycloalkyloxycarbonyl group whichmay have at least a substituent, an aryloxycarbonyl group which may haveat least substituent, a heterocyclic oxycarbonyl group which may have atleast a substituent, a lower alkylsulfonyl group which may have at leasta substituent, a lower alkenylsulfonyl group which may have at least asubstituent, a lower alkynylsulfonyl group which may have at least asubstituent, a lower cycloalkylsulfonyl group which may have at least asubstituent, an arylsulfonyl group which may have at least asubstituent, a heterocyclic sulfonyl group which may have at least asubstituent, an aminocarbonyl group, a lower alkylaminocarbonyl groupwhich may have at least a substituent, a lower alkenylaminocarbonylgroup which may have at least a substituent, a loweralkynylaminocarbonyl group which may have at least a substituent, alower cycloalkylaminocarbonyl group which may have at least asubstituent, an arylaminocarbonyl group which may have at least asubstituent or a heterocyclic aminocarbonyl group which may have atleast a substituent;

in the case where R⁷ is NR⁸R⁹, R⁸ and R⁹ may be combined together toform a 3- to 8-membered nitrogen-containing heterocyclic ring which mayhave at least a substituent; and

X represents O or S. Hereinafter the same shall apply.]

Advantage of the Invention

The present invention provides a 1,2,3,4-tetrahydroquinoxalinederivative or a salt thereof, which is useful as a pharmaceutical. Thepresent compound has an excellent glucocorticoid receptor bindingactivity and is useful as a glucocorticoid receptor modulator. Inparticular, the present compound is useful as a preventive ortherapeutic agent for glucocorticoid action related diseases, that is,metabolic disorders such as diabetes and obesity, inflammatory diseasessuch as arthritis, enteritis and chronic obstructive pulmonary diseases,autoimmune diseases such as connective tissue diseases, allergicdiseases such as asthma, atopic dermatitis, allergic rhinitis andconjunctivitis, central nervous system diseases such as psychiatricdisorders, Alzheimer's disease and drug use disorders, cardiovasculardiseases such as hypertension, hypercalcemia, hyperinsulinemia andhyperlipidemia, homeostasis-related diseases causing an abnormality ofneuro-immune-endocrine balance, glaucoma and the like.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, definitions of terms and phrases (atoms, groups, rings andthe like) to be used in this specification will be described in detail.

The “halogen atom” refers to a fluorine, chlorine, bromine or iodineatom.

The “lower alkyl group” refers to a straight chain or branched alkylgroup having 1 to 8 carbon atoms. Specific examples thereof includemethyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl,isopropyl, isobutyl, sec-butyl, tert-butyl and isopentyl groups and thelike.

The “lower alkenyl group” refers to a straight chain or branched alkenylgroup having 2 to 8 carbon atoms. Specific examples thereof includevinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl,isopropenyl, 2-methyl-1-propenyl and 2-methyl-2 butenyl groups and thelike.

The “lower alkynyl group” refers to a straight chain or branched alkynylgroup having 2 to 8 carbon atoms. Specific examples thereof includeethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl,isobutynyl and isopentynyl groups and the like.

The “lower cycloalkyl group” refers to a cycloalkyl group having 3 to 8carbon atoms. Specific examples thereof include cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl groups.

The “lower cycloalkane ring” refers to a cycloalkane ring having 3 to 8carbon atoms. Specific examples thereof include cyclopropane,cyclobutane, cyclopentane, cyclohexane, cycloheptane and cyclooctanerings.

The “aryl group” refers to a residue formed by removing one hydrogenatom from a monocyclic aromatic hydrocarbon group, or bicyclic ortricyclic condensed polycyclic aromatic hydrocarbon having 6 to 14carbon atoms. Further, A residue formed by removing one hydrogen atomfrom bicyclic or tricyclic condensed polycyclic hydrocarbon having 6 to14 carbon atoms is also included in the scope of the “aryl group”.Specific examples thereof include phenyl, naphthyl, anthryl, phenanthryland fluorenyl groups and the like.

The “heterocyclic group” refers to a residue formed by removing onehydrogen atom from a saturated or unsaturated monocyclic heterocyclicring, or a bicyclic or tricyclic condensed polycyclic heterocyclic ringhaving one or a plurality of heteroatoms selected from a nitrogen atom,an oxygen atom and a sulfur atom in the ring.

Specific examples of the saturated monocyclic heterocyclic ring includepyrrolidine, pyrazolidine, imidazolidine, triazolidine, piperidine,hexahydropyridazine, hexahydropyrimidine, piperazine, homopiperidine andhomopiperazine rings and the like having a nitrogen atom in the ring,tetrahydrofuran and tetrahydropyran rings and the like having an oxygenatom in the ring, tetrahydrothiophene and tetrahydrothiopyran rings andthe like having a sulfur atom in the ring, oxazolidine, isoxazolidineand morpholine rings and the like having a nitrogen atom and an oxygenatom in the ring, and thiazolidine, isothiazolidine and thiomorpholinerings and the like having a nitrogen atom and a sulfur atom in the ring.

Further, such a saturated monocyclic heterocyclic ring can be condensedwith a benzene ring or the like to form a bicyclic or tricycliccondensed polycyclic heterocyclic ring such as a dihydroindole,dihydroindazole, dihydrobenzimidazole, tetrahydroquinoline,tetrahydroisoquinoline, tetrahydrocinnoline, tetrahydrophthalazine,tetrahydroquinazoline, tetrahydroquinoxaline, dihydrobenzofuran,dihydroisobenzofuran, chromane, isochromane, dihydrobenzothiophene,dihydroisobenzothiophene, thiochromane, isothiochromane,dihydrobenzoxazole, dihydrobenzisoxazole, dihydrobenzoxazine,dihydrobenzothiazole, dihydrobenzisothiazole, dihydrobenzothiazine,xanthene, 4a-carbazole and perimidine rings and the like.

Specific examples of the unsaturated monocyclic heterocyclic ringinclude dihydropyrrole, pyrrole, dihydropyrazole, pyrazole,dihydroimidazole, imidazole, dihydrotriazole, triazole,tetrahydropyridine, dihydropyridine, pyridine, tetrahydropyridazine,dihydropyridazine, pyridazine, tetrahydropyrimidine, dihydropyrimidine,pyrimidine, tetrahydropyrazine, dihydropyrazine and pyrazine rings andthe like having a nitrogen atom in the ring, dihydrofuran, furan,dihydropyran and pyran rings and the like having an oxygen atom in thering, dihydrothiophene, thiophene, dihydrothiopyran and thiopyran ringsand the like having a sulfur atom in the ring, dihydrooxazole, oxazole,dihydroisoxazole, isoxazole, dihydrooxazine and oxazine rings and thelike having a nitrogen atom and an oxygen atom in the ring,dihydrothiazole, thiazole, dihydroisothiazole, isothiazole,dihydrothiazine and thiazine rings and the like having a nitrogen atomand a sulfur atom in the ring.

Further, such an unsaturated monocyclic heterocyclic ring can becondensed with a benzene ring or the like to form a bicyclic ortricyclic condensed polycyclic heterocyclic ring such as an indole,indazole, benzimidazole, benzotriazole, dihydroquinoline, quinoline,dihydroisoquinoline, isoquinoline, phenanthridine, dihydrocinnoline,cinnoline, dihydrophthalazine, phthalazine, dihydroquinazoline,quinazoline, dihydroquinoxaline, quinoxaline, benzofuran, isobenzofuran,chromene, isochromene, benzothiophene, isobenzothiophene, thiochromene,isothiochromene, benzoxazole, benzisoxazole, benzoxazine, benzothiazole,benzisothiazole, benzothiazine, phenoxanthin, carbazole, β-carboline,phenanthridine, acridine, phenanthroline, phenazine, phenothiazine orphenoxazine rings and the like.

The “lower alkoxy group” refers to a group formed by replacing thehydrogen atom of a hydroxy group with a lower alkyl group. Specificexamples thereof include methoxy, ethoxy, n-propoxy, n-butoxy,n-pentoxy, n-hexyloxy, n-heptyloxy, n-octyloxy, isopropoxy, isobutoxy,sec-butoxy, tert-butoxy and isopentoxy groups and the like.

The “lower alkenyloxy group” refers to a group formed by replacing thehydrogen atom of a hydroxy group with a lower alkenyl group. Specificexamples thereof include vinyloxy, propenyloxy, butenyloxy, pentenyloxy,hexenyloxy, heptenyloxy, octenyloxy, isopropenyloxy,2-methyl-1-propenyloxy and 2-methyl-2-butenyloxy groups and the like.

The “lower alkynyloxy group” refers to a group formed by replacing thehydrogen atom of a hydroxy group with a lower alkynyl group. Specificexamples thereof include ethynyloxy, propynyloxy, butynyloxy,pentynyloxy, hexynyloxy, heptynyloxy, octynyloxy, isobutynyloxy andisopentynyloxy groups and the like.

The “lower cycloalkyloxy group” refers to a group formed by replacingthe hydrogen atom of a hydroxy group with a lower cycloalkyl group.Specific examples thereof include cyclopropyloxy, cyclobutyloxy,cyclopentyloxy, cyclohexyloxy, cycloheptyloxy and cyclooctyloxy groups.

The “aryloxy group” refers to a group formed by replacing the hydrogenatom of a hydroxy group with an aryl group. Specific examples thereofinclude phenoxy, naphthoxy, anthryloxy and phenanthryloxy groups and thelike.

The “heterocyclic oxy group” refers to a group formed by replacing thehydrogen atom of a hydroxy group with a heterocyclic group.

The “lower alkylthio group” refers to a group formed by replacing thehydrogen atom of a mercapto group with a lower alkyl group. Specificexamples thereof include methylthio, ethylthio, n-propylthio,n-butylthio, n-pentylthio, n-hexylthio, n-heptylthio, n-octylthio,isopropylthio, isobutylthio, sec-butylthio, tert-butylthio andisopentylthio groups and the like.

The “lower cycloalkylthio group” refers to a group formed by replacingthe hydrogen atom of a mercapto group with a lower cycloalkyl group.Specific examples thereof include cyclopropylthio, cyclobutylthio,cyclopentylthio, cyclohexylthio, cycloheptylthio and cyclooctylthiogroups.

The “arylthio group” refers to a group formed by replacing the hydrogenatom of a mercapto group with an aryl group. Specific examples thereofinclude phenylthio, naphthylthio, anthrylthio and phenanthrylthio groupsand the like.

The “heterocyclic thio group” refers to a group formed by replacing thehydrogen atom of a mercapto group with a heterocyclic group.

The “lower alkylamino group” refers to a group formed by replacing oneor both of the hydrogen atoms of an amino group with a lower alkylgroup. Specific examples thereof include methylamino, ethylamino,propylamino, dimethylamino, diethylamino and ethyl(methyl)amino groupsand the like.

The “lower cycloalkylamino group” refers to a group formed by replacingone or both of the hydrogen atoms of an amino group with a lowercycloalkyl group, or a group formed by replacing one of the hydrogenatoms of an amino group with a lower cycloalkyl group and the otherhydrogen atom with a lower alkyl group, a lower alkenyl group or a loweralkynyl group. Specific examples thereof include cyclopropylamino,cyclobutylamino, cyclopentylamino, cyclohexylamino, cycloheptylamino,cyclooctylamino, dicyclohexylamino, cyclohexyl(methyl)amino,cyclohexyl(vinyl)amino and cyclohexyl(ethynyl)amino groups and the like.

The “arylamino group” refers to a group formed by replacing one or bothof the hydrogen atoms of an amino group with an aryl group, or a groupformed by replacing one of the hydrogen atoms of an amino group with anaryl group and the other hydrogen atom with a lower alkyl group, a loweralkenyl group, a lower alkynyl group or a lower cycloalkyl group.Specific examples thereof include phenylamino, naphthylamino,anthrylamino, phenanthrylamino, diphenylamino, methyl(phenyl)amino,ethyl(phenyl)amino, phenyl(vinyl)amino, ethynyl(phenyl)amino andcyclohexyl(phenyl)amino groups and the like.

The “heterocyclic amino group” refers to a group formed by replacing oneor both of the hydrogen atoms of an amino group with a heterocyclicgroup, or a group formed by replacing one of the hydrogen atoms of anamino group with a heterocyclic group and the other hydrogen atom with alower alkyl group, a lower alkenyl group, a lower alkynyl group, a lowercycloalkyl group or an aryl group.

The “lower alkylcarbonyl group” refers to a group formed by replacingthe hydrogen atom of a formyl group with a lower alkyl group. Specificexamples thereof include methylcarbonyl, ethylcarbonyl,n-propylcarbonyl, n-butylcarbonyl, n-pentylcarbonyl, n-hexylcarbonyl,n-heptylcarbonyl, n-octylcarbonyl, isopropylcarbonyl, isobutylcarbonyl,sec-butylcarbonyl, tert-butylcarbonyl and isopentylcarbonyl groups andthe like.

The “lower alkenylcarbonyl group” refers to a group formed by replacingthe hydrogen atom of a formyl group with a lower alkenyl group. Specificexamples thereof include vinylcarbonyl, propenylcarbonyl,butenylcarbonyl, pentenylcarbonyl, hexenylcarbonyl, heptenylcarbonyl,octenylcarbonyl, isopropenylcarbonyl, 2-methyl-1-propenylcarbonyl and2-methyl-2-butenylcarbonyl groups and the like.

The “lower alkynylcarbonyl group” refers to a group formed by replacingthe hydrogen atom of a formyl group with a lower alkynyl group. Specificexamples thereof include ethynylcarbonyl, propynylcarbonyl,butynylcarbonyl, pentynylcarbonyl, hexynylcarbonyl, heptynylcarbonyl,octynylcarbonyl, isobutynylcarbonyl and isopentynylcarbonyl groups andthe like.

The “lower cycloalkylcarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a lower cycloalkylgroup. Specific examples thereof include cyclopropylcarbonyl,cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl,cycloheptylcarbonyl and cyclooctylcarbonyl groups.

The “arylcarbonyl group” refers to a group formed by replacing thehydrogen atom of a formyl group with an aryl group. Specific examplesthereof include phenylcarbonyl, naphthylcarbonyl, anthrylcarbonyl andphenanthrylcarbonyl groups and the like.

The “heterocyclic carbonyl group” refers to a group formed by replacingthe hydrogen atom of a formyl group with a heterocyclic group.

The “lower alkoxycarbonyl group” refers to a group formed by replacingthe hydrogen atom of a formyl group with a lower alkoxy group. Specificexamples thereof include methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, n-butoxycarbonyl, n-pentoxycarbonyl,n-hexyloxycarbonyl, n-heptyloxycarbonyl, n-octyloxycarbonyl,isopropoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl,tert-butoxycarbonyl and isopentoxycarbonyl groups and the like.

The “lower alkenyloxycarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a lower alkenyloxygroup. Specific examples thereof include vinyloxycarbonyl,propenyloxycarbonyl, butenyloxycarbonyl, pentenyloxycarbonyl,hexenyloxycarbonyl, heptenyloxycarbonyl, octenyloxycarbonyl,isopropenyloxycarbonyl, 2-methyl-1-propenyloxycarbonyl and2-methyl-2-butenyloxycarbonyl groups and the like.

The “lower alkynyloxycarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a lower alkynyloxygroup. Specific examples thereof include ethynyloxycarbonyl,propynyloxycarbonyl, butynyloxycarbonyl, pentynyloxycarbonyl,hexynyloxycarbonyl, heptynyloxycarbonyl, octynyloxycarbonyl,isobutynyloxycarbonyl and isopentynyloxycarbonyl groups and the like.

The “lower cycloalkyloxycarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a lower cycloalkyloxygroup. Specific examples thereof include cyclopropyloxycarbonyl,cyclobutyloxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl,cycloheptyloxycarbonyl and cyclooctyloxycarbonyl groups.

The “aryloxycarbonyl group” refers to a group formed by replacing thehydrogen atom of a formyl group with an aryloxy group. Specific examplesthereof include phenoxycarbonyl, naphthoxycarbonyl, anthryloxycarbonyland phenanthryloxycarbonyl groups and the like.

The “heterocyclic oxycarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a heterocyclic oxygroup.

The “lower alkylaminocarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a lower alkylaminogroup. Specific examples thereof include methylaminocarbonyl,ethylaminocarbonyl, propylaminocarbonyl, dimethylaminocarbonyl,diethylaminocarbonyl and ethylmethylaminocarbonyl groups and the like.

The “lower alkenylaminocarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a lower alkenylaminogroup. Specific examples thereof include vinylaminocarbonyl,propenylaminocarbonyl, butenylaminocarbonyl, pentenylaminocarbonyl,hexenylaminocarbonyl, heptenylaminocarbonyl, octenylaminocarbonyl,isopropenylaminocarbonyl, 2-methyl-1-propenylaminocarbonyl,2-methyl-2-butenylaminocarbonyl, divinylaminocarbonyl andmethyl(vinyl)aminocarbonyl groups and the like.

The “lower alkynylaminocarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a lower alkynylaminogroup. Specific examples thereof include ethynylaminocarbonyl,propynylaminocarbonyl, butynylaminocarbonyl, pentynylaminocarbonyl,hexynylaminocarbonyl, heptynylaminocarbonyl, octynylaminocarbonyl,isobutynylaminocarbonyl, isopentynylaminocarbonyl,diethynylaminocarbonyl, ethynyl(methyl)aminocarbonyl andethynyl(vinyl)aminocarbonyl groups and the like.

The “lower cycloalkylaminocarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a lowercycloalkylamino group. Specific examples thereof includecyclopropylaminocarbonyl, cyclobutylaminocarbonyl,cyclopentylaminocarbonyl, cyclohexylaminocarbonyl,cycloheptylaminocarbonyl, cyclooctylaminocarbonyl,dicyclohexylaminocarbonyl, cyclohexyl(methyl)aminocarbonyl,cyclohexyl(vinyl)aminocarbonyl and cyclohexyl(ethynyl)aminocarbonylgroups and the like.

The “arylaminocarbonyl group” refers to a group formed by replacing thehydrogen atom of a formyl group with an arylamino group. Specificexamples thereof include phenylaminocarbonyl, naphthylaminocarbonyl,anthrylaminocarbonyl, phenanthrylaminocarbonyl, diphenylaminocarbonyl,methylphenylaminocarbonyl ethylphenylaminocarbonyl,phenyl(vinyl)aminocarbonyl, ethynyl(phenyl)aminocarbonyl andcyclohexyl(phenyl)aminocarbonyl groups and the like.

The “heterocyclic aminocarbonyl group” refers to a group formed byreplacing the hydrogen atom of a formyl group with a heterocyclic aminogroup.

The “lower alkylsulfonyl group” refers group formed by replacing thehydroxy group of a sulfonic acid group with a lower alkyl group.Specific examples thereof include methylsulfonyl, ethylsulfonyl,n-propylsulfonyl, n-butylsulfonyl, n-pentylsulfonyl, n-hexylsulfonyl,n-heptylsulfonyl, n-octylsulfonyl, isopropylsulfonyl, isobutylsulfonyl,sec-butylsulfonyl, tert-butylsulfonyl and isopentylsulfonyl groups andthe like.

The “lower alkenylsulfonyl group” refers to group formed by replacingthe hydroxy group of a sulfonic acid group with a lower alkenyl, group.Specific examples thereof include vinylsulfonyl, propenylsulfonyl,butenylsulfonyl, pentenylsulfonyl, hexenylsulfonyl, heptenylsulfonyl,octenylsulfonyl, isopropenylsulfonyl, 2-methyl-1-propenylsulfonyl and2-methyl-2-butenylsulfonyl groups and the like.

The “lower alkynylsulfonyl group” refers to a group formed by replacingthe hydroxy group of a sulfonic acid group with a lower alkynyl group.Specific examples thereof include ethynylsulfonyl, propynylsulfonyl,butynylsulfonyl, pentynylsulfonyl, hexynylsulfonyl, heptynylsulfonyl,octynylsulfonyl, isobutynylsulfonyl and isopentynylsulfonyl groups andthe like.

The “lower cycloalkylsulfonyl group” refers to a group formed byreplacing the hydroxy group of a sulfonic acid group with a lowercycloalkyl group. Specific examples thereof include cyclopropylsulfonyl,cyclobutylsulfonyl, cyclopentylsulfonyl, cyclohexylsulfonyl,cycloheptylsulfonyl and cyclooctylsulfonyl groups.

The “arylsulfonyl group” refers to a group formed by replacing thehydroxy group of a sulfonic acid group with an aryl group. Specificexamples thereof include phenylsulfonyl, naphthylsulfonyl,anthrylsulfonyl and phenanthrylsulfonyl groups and the like.

The “heterocyclic sulfonyl group” refers to a group formed by replacingthe hydroxy group of a sulfonic acid group with a heterocyclic group.

The “3- to 8-membered nitrogen-containing heterocyclic ring” refers to asaturated monocyclic heterocyclic ring containing one or two nitrogenatoms in the ring. Specific examples thereof include aziridine,azetidine, pyrrolidine, imidazolidine, pyrazolidine, piperazine andmorpholine rings and the like.

The “lower alkylene group” refers to a straight chain or branchedalkylene group having 1 to 8 carbon atoms. Specific examples thereofinclude methylene, ethylene, trimethylene, tetramethylene,pentamethylene, hexamethylene, heptamethylene, octamethylene,methylmethylene and ethylmethylene groups and the like.

The “ester of a hydroxy group” refers to an ester formed from a hydroxygroup and a carboxylic acid and/or a group represented by —OCO—R.

Herein, R represents a hydrogen atom, a lower alkyl group which may haveat least a substituent, a lower alkenyl group which may have at least asubstituent, a lower alkynyl group which may have at least asubstituent, a lower cycloalkyl group which may have at least asubstituent, an aryl group which may have at least a substituent, aheterocyclic group which may have at least a substituent, a lower alkoxygroup which may have at least a substituent, a lower alkenyloxy groupwhich may have at least a substituent, a lower alkynyloxy group whichmay have at least a substituent, a lower cycloalkyloxy group which mayhave at least a substituent, an aryloxy group which may have at least asubstituent, a heterocyclic oxy group which may have at least asubstituent, an amino group, a lower alkylamino group which may have atleast a substituent, a lower cycloalkylamino group which may have atleast a substituent, an arylamino group which may have at least asubstituent or a heterocyclic amino group which may have at least asubstituent. R is the same as below.

The “ester of a mercapto group” refers to a thioester formed from amercapto group and a carboxylic acid and/or a group represented by—SCO—R. Herein, R is the same as the above.

The “amide of an amino group” refers to an amide formed from an aminogroup and a carboxylic acid and/or a group represented by —NHCO—R.Herein, R is the same as the above.

The “amide of a lower alkylamino group” refers to an amide formed from alower alkylamino group and a carboxylic acid and/or a group representedby —NR′CO—R. Herein, R′ represents a lower alkyl group which may have atleast a substituent, and R is the same as the above.

The “amide of a lower cycloalkylamino group” refers to an amide formedfrom a lower cycloalkylamino group and a carboxylic acid and/or a grouprepresented by —NR″CO—R. Herein, R″ represents a lower cycloalkyl groupwhich may have at least a substituent, and R is the same as the above.

The “amide of an arylamino group” refers to an amide formed from anarylamino group and a carboxylic acid and/or a group represented by—NR′″CO—R. Herein, R′″ represents an aryl group which may have at leasta substituent, and R is the same as the above.

The “amide of a heterocyclic amino group” refers to an amide formed froma heterocyclic amino group and a carboxylic acid and/or a grouprepresented by —NR″″CO—R. Herein, R″″ represents a heterocyclic groupwhich may have at least a substituent, and R is the same for the above.

The “carboxylic acid” refers to a saturated aliphatic carboxylic acid,an unsaturated aliphatic carboxylic acid, an aryl carboxylic acid, aheterocyclic carboxylic acid or the like represented by R^(a)COOH (R^(a)represents a hydrogen atom, a lower alkyl group which may have at leasta substituent, a lower alkenyl group which may have at least asubstituent, a lower alkynyl group which may have at least asubstituent, a lower cycloalkyl group which may have at least asubstituent, an aryl group which may have at least a substituent, aheterocyclic group which may have at least a substituent and the like).Specific examples thereof include saturated aliphatic carboxylic acidssuch as formic acid, acetic acid, propionic acid, butyric acid,isobutyric acid, valeric acid, isovaleric acid, pivalic acid,cyclopropanecarboxylic acid, cyclobutanecarboxylic acid,cyclopentanecarboxylic acid and cyclohexanecarboxylic acid; unsaturatedaliphatic carboxylic acids such as acrylic acid, propionic acid,crotonic acid, cinnamic acid, cyclopentenecarboxylic acid andcyclohexenecarboxylic acid; aryl carboxylic acids such as benzoic acid,phthalic acid, isophthalic acid, terephthalic acid, naphthoic acid andtoluic acid; heterocyclic carboxylic acids such as furancarboxylic acid,thiophenecarboxylic acid, nicotinic acid and isonicotinic acid; and thelike.

The “ester of a carboxy group” refers to an ester formed from a carboxygroup and an alcohol or a phenol.

The “ester of a sulfonic acid group” refers to an ester formed from asulfonic acid group and an alcohol or a phenol.

The “alcohol” refers to a saturated aliphatic hydroxy compound, anunsaturated aliphatic hydroxy compound, a heterocyclic hydroxyl compoundor the like represented by R^(b)OH (R^(b) represents a lower alkyl groupwhich may have at least a substituent, a lower alkenyl group which mayhave at least a substituent, a lower alkynyl group which may have atleast a substituent, a lower cycloalkyl group which may have at least asubstituent, a heterocyclic group which may have at least a substituentor the like). Specific examples thereof include saturated aliphatichydroxy compounds such as methanol, ethanol, propanol, butanol,isopropanol, cyclopropanol, cyclobutanol, cyclopentanol, cyclohexanol,benzylalcohol and phenethylalcohol; unsaturated aliphatic hydroxycompounds such as vinyl alcohol, allylalcohol, propagylalcohol,cyclopentenol and cyclohexenol; heterocyclic hydroxy compounds such ashydroxypiperidine and hydroxytetrahydropyran.

The “phenol” refers to an aryl hydroxy compound, a heterocyclic hydroxylcompound or the like represented by R^(c)OH (R^(c) represents an arylgroup which may have at least a substituent, a heterocyclic group whichmay have at least a substituent or the like). Specific examples thereofinclude aryl hydroxyl compounds such as phenol, naphthol, anthrol andphenanthrol; heterocyclic hydroxyl compounds such as hydroxypyridine,hydroxyfuran and hydroxythiophen.

The “amide of a carboxy group” refers to an acid amide formed from acarboxy group and an amine.

The “amide of a sulfonic acid group” refers to an acid amide formed froma sulfonic acid group and an amine.

The “amine” refers to ammonia, a saturated aliphatic amine compound, anunsaturated aliphatic amine compound, an aryl amine compound,heterocyclic amine compound, a saturated cyclic amine compound or thelike represented by HNR^(d)R^(e) (R^(d) and R^(e) may be the same ordifferent and represent a hydrogen atom, a lower alkyl group which mayhave at least a substituent, a lower alkenyl group which may have atleast a substituent, a lower alkynyl group which may have at least asubstituent, a lower cycloalkyl group which may have at least asubstituent, an aryl group which may have at least a substituent, aheterocyclic group or the like, or R^(d) and R^(e) may be combinedtogether to form a saturated cyclic amine). Specific examples thereofinclude ammonia; saturated aliphatic amine compounds such asmethylamine, ethylamine, propylamine, pentylamine, dimethylamine,diethylamine, ethylmethylamine, cyclopropylamine, cyclobutylamine,cyclopentylamine, cyclohexylamine, benzylamine and phenetylamine;unsaturated aliphatic amine compounds such as allylamine andpropagylamine; aryl amine compounds such as phenylamine, naphthylamine,anthrylamine, phenanthrylamine, diphenylamine, methylphenylamine andethylphenylamine; heterocyclic amine compounds such as furylamine,thienylamine, pyrrolidylamine, pyridylamine, quinolylamine andmethylpyridylamine; saturated cyclic amine compounds such as aziridine,azetidine, pyrrolidine, piperidine and 4-methylpiperidine.

The “lower alkyl group which may have at least a substituent”, “loweralkenyl group which may have at least a substituent”, “lower alkynylgroup which may have at least a substituent”, “lower alkoxy group whichmay have at least a substituent”, “lower alkyltio group which may haveat least a substituent”, “lower alkylamino group which may have at leasta substituent”, “lower alkylcarbonyl group which may have at least asubstituent”, “lower alkenylcarbonyl group which may have at least asubstituent”, “lower alkynylcarbonyl group which may have at least asubstituent”, “lower alkoxycarbonyl group which may have at least asubstituent”, “lower alkenyloxycarbonyl group which may have at least asubstituent”, “lower alkynyloxycarbonyl group which may have at least asubstituent”, “lower alkylaminocarbonyl group which may have at least asubstituent”, “lower alkenylaminocarbonyl group which may have at leasta substituent”, “lower alkynylaminocarbonyl group which may have atleast a substituent”, “lower alkylsulfonyl group which may have at leasta substituent”, “lower alkenylsulfonyl group which may have at least asubstituent”, “lower alkynylsulfonyl group which may have at least asubstituent” and “amide of lower alkylamino group which may have atleast a substituent” refer to a “lower alkyl group”, a “lower alkenylgroup”, a “lower alkynyl group”, a “lower alkoxy group”, a “loweralkylthio group”, a “lower alkylamino group”, a “lower alkylcarbonylgroup”, a “lower alkenylcarbonyl group”, a “lower alkynylcarbonylgroup”, a “lower alkoxycarbonyl group”, a “lower alkenyloxycarbonylgroup”, a “lower alkynyloxycarbonyl group”, a “lower alkylaminocarbonylgroup”, a “lower alkenylaminocarbonyl group”, a “loweralkynylaminocarbonyl group”, a “lower alkylsulfonyl group”, a “loweralkenylsulfonyl group”, a “lower alkynylsulfonyl group” and an “amide ofthe lower alkylamino group” which may have one or a plurality ofsubstituents selected from the following α¹ group, respectively.

[α¹ Group]

A halogen atom, a lower cycloalkyl group, an aryl group, a heterocyclicgroup, a hydroxy group, an ester of a hydroxy group, a lower alkoxygroup, a lower alkoxy group substituted by a halogen atom, a loweralkenyloxy group, a lower alkynyloxy group, a lower cycloalkyloxy group,an aryloxy group, a heterocyclic oxy group, a mercapto group, an esterof a mercapto group, a lower alkylthio group, a lower alkenylthio group,a lower alkynylthio group, a lower cycloalkylthio group, an arylthiogroup, a heterocyclic thio group, an amino group, a lower alkylaminogroup, a lower cycloalkylamino group, an arylamino group, a heterocyclicamino group, an amide of an amino group, an amide of a lower alkylaminogroup, an amide of a lower cycloalkylamino group, an amide of anarylamino group, an amide of a heterocyclic amino group, a formyl group,a lower alkylcarbonyl group, a lower alkenylcarbonyl group, a loweralkynylcarbonyl group, a lower cycloalkylcarbonyl group, an arylcarbonylgroup, a heterocyclic carbonyl group, a carboxy group, an ester of acarboxy group, an amide of a carboxy group, a lower alkylsulfinyl group,an arylsulfinyl group, a lower alkylsulfonyl group, a lowercycloalkylsulfonyl group, an arylsulfonyl group, a heterocyclic sulfonylgroup, a sulfinic acid group, an ester of a sulfinic acid group, anamide of a sulfinic acid group, a sulfonic acid group, an ester of asulfonic acid group, an amide of a sulfonic acid group, a nitro groupand a cyano group.

The “lower cycloalkyl group which may have at least a substituent”,“aryl group which may have at least a substituent”, “heterocyclic groupwhich may have at least a substituent”, “lower cycloalkyloxy group whichmay have at least a substituent”, “aryloxy group which may have at leasta substituent”, “heterocyclic oxy group which may have at least asubstituent”, “lower cycloalkylthio group which may have at least asubstituent”, “arylthio group which may have at least a substituent”,“heterocyclic thio group which may have at least substituent”, “lowercycloalkylamino group which may have at least a substituent”, “arylaminogroup which may have at least a substituent”, “heterocyclic amino groupwhich may have at least a substituent”, “lower cycloalkylcarbonyl groupwhich may have at least a substituent”, “arylcarbonyl group which mayhave at least a substituent”, “heterocyclic carbonyl group which mayhave at least a substituent”, “lower cycloalkyloxycarbonyl group whichmay have at least a substituent”, “aryloxycarbonyl group which may haveat least a substituent”, “heterocyclic oxycarbonyl group which may haveat least a substituent”, “lower cycloalkylaminocarbonyl group which mayhave at least a substituent”, “arylaminocarbonyl group which may have atleast a substituent”, “heterocyclic aminocarbonyl group which may haveat least a substituent”, “lower cycloalkylsulfonyl group which may haveat least a substituent”, “arylsulfonyl group which may have at least asubstituent”, “heterocyclic sulfonyl group which may have at least asubstituent”, “amide of lower cycloalkylamino group which may have atleast a substituent”, “amide of arylamino group which may have at leasta substituent” and “amide of heterocyclic amino group which may have atleast a substituent” refer to a “lower cycloalkyl group”, an “arylgroup”, a “heterocyclic group”, a “lower cycloalkyloxy group”, an“aryloxy group”, a “heterocyclic oxy group”, a “lower cycloalkylthiogroup”, an “arylthio group”, “heterocyclic thio group”, a “lowercycloalkylamino group”, an “arylamino group”, a “heterocyclic aminogroup”, a “lower cycloalkylcarbonyl group”, an “arylcarbonyl group”, a“heterocyclic carbonyl group”, an “lower cycloalkyloxycarbonyl group”,an “aryloxycarbonyl group”, a “heterocyclic oxycarbonyl group”, a “lowercycloalkylaminocarbonyl group”, an “arylaminocarbonyl group”, a“heterocyclic aminocarbonyl group”, a “lower cycloalkylsulfonyl group”,an “arylsulfonyl group”, a “heterocyclic sulfonyl group”, an “amide oflower cycloalkylamino group”, an “amide of arylamino group” and an“amide of heterocyclic amino group” which may have one or a plurality ofsubstituents selected from the following β¹ group, respectively.

[β¹ Group]

A halogen atom, a lower alkyl group, a lower alkyl group substituted bya halogen atom, a lower alkenyl group, a lower alkynyl group, a lowercycloalkyl group, an aryl group, a heterocyclic group, a hydroxy group,an ester of a hydroxy group, a lower alkoxy group, lower alkoxy groupsubstituted by a halogen atom, a lower alkenyloxy group, a loweralkynyloxy group, a lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a mercapto group, an ester of a mercapto group,a lower alkylthio group, a lower alkenylthio group, lower alkynylthiogroup, a lower cycloalkylthio group, an arylthio group, a heterocyclicthio group, an amino group, a lower alkylamino group, a lowercycloalkylamino group, an arylamino group, a heterocyclic amino group,an amide of an amino group, an amide of a lower alkylamino group, anamide of a lower cycloalkylamino group, an amide of an arylamino group,an amide of a heterocyclic amino group, a formyl group, a loweralkylcarbonyl group, a lower alkenylcarbonyl group, a loweralkynylcarbonyl group, a lower cycloalkylcarbonyl group, an arylcarbonylgroup, a heterocyclic carbonyl group, a carboxy group, an ester of acarboxy group, an amide of a carboxy group, a lower alkylsulfinyl group,an arylsulfinyl group, a lower alkylsulfonyl group, a lowercycloalkylsulfonyl group, an arylsulfonyl group, a heterocyclic sulfonylgroup, a sulfinic acid group, an ester of a sulfinic acid group, anamide of a sulfinic acid group, a sulfonic acid group, an ester of asulfonic acid group, an amide of a sulfonic acid group, a nitro group, acyano group, lower alkylaminocarbonyloxy group and anarylaminocarbonyloxy group.

The term “a plurality of groups” as used herein means that each groupmay be the same or different and the number of groups is preferably 2.Further, a hydrogen atom and a halogen atom are also included in theconcept of the “group”.

The “glucocorticoid receptor modulator” as used herein refers to amodulator that exhibits a pharmaceutical action by binding toglucocorticoid receptor. Examples thereof include glucocorticoidreceptor agonists, glucocorticoid receptor antagonists and the like.

The “salt” of the present compound is not particularly limited as longas it is pharmaceutically acceptable salt, and examples thereof includesalts with an inorganic acid such as hydrochloric acid, hydrobromicacid, hydroiodic acid, nitric acid, sulfuric acid or phosphoric acid;salts with an organic acid such as acetic acid, fumalic acid, maleicacid, succinic acid, citric acid, tartaric acid, adipic acid, gluconicacid, glucoheptonic acid, glucuronic acid, terephthalic acid,methanesulfonic acid, lactic acid, hippuric acid, 1,2-ethanedisulfonicacid, isethionic acid, lactobionic acid, oleic acid, pamoic acid,polygalacturonic acid, stearic acid, tannic acid,trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonicacid, lauryl sulfate ester, methyl sulfate, naphthalenesulfonic acid orsulfosalicylic acid; quaternary ammonium salts with methyl bromide,methyl iodide or the like; salts with a halogen ion such as a bromineion, a chlorine ion or an iodine ion; salts with an alkali metal such aslithium, sodium or potassium; salts with an alkaline earth metal such ascalcium or magnesium; salts with a metal such as iron or zinc; saltswith ammonia; salts with an organic amine such as triethylenediamine,2-aminoethanol, 2,2-iminobis(ethanol),1-deoxy-1-(methylamino)-2-D-sorbitol,2-amino-2-(hydroxymethyl)-1,3-propanediol, procaine orN,N-bis(phenylmethyl)-1,2-ethanediamine; and the like.

In the case where there are geometrical isomers or optical isomers inthe present compound, these isomers are also included in the scope ofthe present invention.

Further, the present compound may be in the form of a hydrate or asolvate.

In the case where there is proton tautomerism in the present compound,the tautomeric isomers thereof are also included in the presentinvention.

In the case where there are crystalline polymorphisms in the presentcompound, the crystalline polymorphisms thereof are also included in thepresent invention.

(a) Preferred examples of the present compound include compounds inwhich the respective groups are groups as defined below and saltsthereof in the compounds represented by the general formula (1) andsalts thereof.

In the general formula (1),

(a1) R¹ represents a halogen atom, a lower alkyl group, a lowercycloalkyl group, an aryl group, a heterocyclic group, a hydroxy group,an ester of a hydroxy group, a lower alkoxy group, a lower cycloalkyloxygroup, an aryloxy group, a heterocyclic oxy group, a mercapto group, anester of a mercapto group, a lower alkylthio group, a lowercycloalkylthio group, an arylthio group, a heterocyclic thio group, anamino group, a lower alkylamino group, a lower cycloalkylamino group, anarylamino group, a heterocyclic amino group, an amide of an amino group,an amide of a lower alkylamino group, an amide of a lowercycloalkylamino group, an amide of an arylamino group, an amide of aheterocyclic amino group, a lower alkylcarbonyl group, a lowercycloalkylcarbonyl group, an arylcarbonyl group, a heterocyclic carbonylgroup, a carboxy group, an ester of a carboxy group, an amide of acarboxy group, a lower alkylsulfonyl group, a lower cycloalkylsulfonylgroup, an arylsulfonyl group, a heterocyclic sulfonyl group, a sulfonicacid group, an ester of a sulfonic acid group, an amide of a sulfonicacid group, a nitro group or a cyano group;

in the case where R¹ is a lower alkyl group, a lower alkoxy group, alower alkylthio group, a lower alkylamino group, an amide of a loweralkylamino group, a lower alkylcarbonyl group or a lower alkylsulfonylgroup, the lower alkyl group, lower alkoxy group, lower alkylthio group,lower alkylamino group, amide of a lower alkylamino group, loweralkylcarbonyl group or lower alkylsulfonyl group may have one or aplurality of groups selected from a halogen atom, a lower cycloalkylgroup, an aryl group, a heterocyclic group, a hydroxy group, an ester ofa hydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith a halogen atom, lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a lower alkylthio group, lower cycloalkylthiogroup, an arylthio group, a heterocyclic thio group, an amino group, alower alkylamino group, lower cycloalkylamino group, an arylamino group,a heterocyclic amino group, an amide of an amino group, an amide of alower alkylamino group, an amide of a lower cycloalkylamino group, anamide of an arylamino group, an amide of a heterocyclic amino group, alower alkylcarbonyl group, a lower cycloalkylcarbonyl group, anarylcarbonyl group, a heterocyclic carbonyl group, a carboxy group, anester of a carboxy group, an amide of a carboxy group, a loweralkylsulfonyl group, a lower cycloalkylsulfonyl group, an arylsulfonylgroup, a heterocyclic sulfonyl group, a sulfonic acid group, an ester ofa sulfonic acid group, an amide of a sulfonic acid group, a nitro groupand a cyano group as substituents;

in the case where R¹ is a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a lower cycloalkylthio group, an arylthio group,a heterocyclic thio group, a lower cycloalkylamino group, an arylaminogroup, a heterocyclic amino group, an amide of a lower cycloalkylaminogroup, an amide of an arylamino group, an amide of a heterocyclic aminogroup, a lower cycloalkylcarbonyl group, an arylcarbonyl group, aheterocyclic carbonyl group, a lower cycloalkylsulfonyl group, anarylsulfonyl group or a heterocyclic sulfonyl group, the lowercycloalkyl group, aryl group, heterocyclic group, lower cycloalkyloxygroup, aryloxy group, heterocyclic oxy group, lower cycloalkylthiogroup, arylthio group, heterocyclic thio group, lower cycloalkylaminogroup, arylamino group, heterocyclic amino group, amide of a lowercycloalkylamino group, amide of an arylamino group, amide of aheterocyclic amino group, lower cycloalkylcarbonyl group, arylcarbonylgroup, heterocyclic carbonyl group, lower cycloalkylsulfonyl group,arylsulfonyl group or heterocyclic sulfonyl group may have one or aplurality of groups selected from a halogen atom, a lower alkyl group, alower alkyl group substituted with a halogen atom, a hydroxy group, anester of a hydroxy group, a lower alkoxy group, a lower alkoxy groupsubstituted with a halogen atom, a lower alkylthio group, an aminogroup, a lower alkylamino group, an amide of an amino group, an amide ofa lower alkylamino group, a lower alkylcarbonyl group, a carboxy group,an ester of a carboxy group, an amide of a carboxy group, a loweralkylsulfonyl group, a sulfonic acid group, an ester of a sulfonic acidgroup, an amide of a sulfonic acid group, a nitro group and a cyanogroup as substituents; and/or

(a2) p represents an integer of 0 to 3;

in the case where p is 2 or 3, each R¹ may be the same or different;and/or

(a3) R² represents a halogen atom, a lower alkyl group, a hydroxy groupor a lower alkoxy group; and/or

(a4) q represents an integer of 0 to 2;

in the case where q is 2, each R² may be the same or different;

and/or

(a5) R³ represents a hydrogen atom, a lower alkyl group, a lower alkenylgroup, a lower alkylcarbonyl group, a lower alkenylcarbonyl group or anarylcarbonyl group;

in the case where R³ is a lower alkyl group or a lower alkylcarbonylgroup, the lower alkyl group or lower alkylcarbonyl group may have oneor a plurality of groups selected from a halogen atom and an aryl groupas substituents;

in the case where R³ is an arylcarbonyl group, the arylcarbonyl groupmay have one or a plurality of groups selected from a halogen atom, alower alkyl group, a lower alkyl group substituted with a halogen atom,a lower alkoxy group and a lower alkoxy group substituted with a halogenatom as substituents; and/or

(a6) R⁴ and R⁵ may be the same or different and represent a hydrogenatom, a halogen atom, a lower alkyl group, a lower cycloalkyl group,aryl or heterocyclic group;

in the case where R⁴ or R⁵ is a lower alkyl group, the lower alkyl groupmay have one or a plurality of groups selected from a halogen atom, alower cycloalkyl group, an aryl group, a heterocyclic group, a hydroxygroup, an ester of a hydroxy group, a lower alkoxy group, lower alkoxygroup substituted with a halogen atom, a lower cycloalkyloxy group, anaryloxy group, a heterocyclic oxy group, a lower alkylthio group, alower cycloalkylthio group, an arylthio group, a heterocyclic thiogroup, an amino group, a lower alkylamino group, a lower cycloalkylaminogroup, an arylamino group, a heterocyclic amino group, an amide of anamino group, an amide of a lower alkylamino group, an amide of a lowercycloalkylamino group, an amide of an arylamino group, an amide of aheterocyclic amino group, a lower alkylcarbonyl group, a lowercycloalkylcarbonyl group, an arylcarbonyl group, a heterocyclic carbonylgroup, a carboxy group, an ester of a carboxy group, an amide of acarboxy group, a nitro group and a cyano group as substituents;

in the case where R⁴ or R⁵ is a lower cycloalkyl group, aryl or aheterocyclic group, the lower cycloalkyl group, aryl or heterocyclicgroup may have one or a plurality of groups selected from a halogenatom, a lower alkyl group, a lower alkyl group substituted with ahalogen atom, a hydroxy group, an ester of a hydroxy group, a loweralkoxy group, a lower alkoxy group substituted with a halogen atom, alower alkylthio group, an amino group, a lower alkylamino group, anamide of an amino group, an amide of a lower alkylamino group, a loweralkylcarbonyl group, a carboxy group, an ester of a carboxy group, anamide of a carboxy group, a lower alkylsulfonyl group, a sulfonic acidgroup, an ester of a sulfonic acid group, an amide of a sulfonic acidgroup, a nitro group and a cyano group as substituents;

R⁴ and R⁵ may be combined together to form a 3- to 8-membered lowercycloalkane ring; and/or

(a7) R⁶ represents a hydrogen atom, a lower alkyl group, a lower alkenylgroup, a lower alkynyl group or a lower cycloalkyl group;

in the case where R⁶ is a lower alkyl group, a lower alkenyl group, alower alkynyl group or a lower cycloalkyl group, the lower alkyl group,lower alkenyl group, lower alkynyl group or lower cycloalkyl group mayhave one or a plurality of groups selected from a halogen atom and anaryl group as substituents; and/or

(a8) A represents a lower alkylene group which may be substituted with ahydroxy group or a halogen atom; and/or

(a9) R⁷ represents OR⁸, NR⁸R⁹ or SR⁸;

R⁸ and R⁹ may be the same or different and represent a hydrogen atom, alower alkyl group, a lower alkenyl group, a lower alkynyl group, a lowercycloalkyl group, an aryl group, a heterocyclic group, a formyl group, alower alkylcarbonyl group, a lower alkenylcarbonyl group, a loweralkynylcarbonyl group, a lower cycloalkylcarbonyl group, an arylcarbonylgroup, a heterocyclic carbonyl group, a carboxy group, a loweralkoxycarbonyl group, a lower alkenyloxycarbonyl group, a loweralkynyloxycarbonyl group, a lower cycloalkyloxycarbonyl group, anaryloxycarbonyl group, a heterocyclic oxycarbonyl group, a loweralkylsulfonyl group, a lower alkenylsulfonyl group, a loweralkynylsulfonyl group, a lower cycloalkylsulfonyl group, an arylsulfonylgroup, a heterocyclic sulfonyl group, an aminocarbonyl group, a loweralkylaminocarbonyl group, a lower alkenylaminocarbonyl group, a loweralkynylaminocarbonyl group, a lower cycloalkylaminocarbonyl group, anarylaminocarbonyl group or a heterocyclic aminocarbonyl group;

in the case where R⁸ or R⁹ is a lower alkyl group, a lower alkenylgroup, a lower alkynyl group, a lower alkylcarbonyl group, a loweralkenylcarbonyl group, a lower alkynylcarbonyl group, a loweralkoxycarbonyl group, a lower alkenyloxycarbonyl group, a loweralkynyloxycarbonyl group, a lower alkylsulfonyl group, a loweralkenylsulfonyl group, a lower alkynylsulfonyl group, a loweralkylaminocarbonyl group, a lower alkenylaminocarbonyl group or a loweralkynylaminocarbonyl group, the lower alkyl group, lower alkenyl group,lower alkynyl group, lower alkylcarbonyl group, lower alkenylcarbonylgroup, lower alkynylcarbonyl group, lower alkoxycarbonyl group, loweralkenyloxycarbonyl group, lower alkynyloxycarbonyl group, loweralkylsulfonyl group, lower alkenylsulfonyl group, lower alkynylsulfonylgroup, lower alkylaminocarbonyl group, lower alkenylaminocarbonyl groupor lower alkynylaminocarbonyl group may have one or a plurality ofgroups selected from a halogen atom, a lower cycloalkyl group, an arylgroup, a heterocyclic group, a hydroxy group, an ester of a hydroxygroup, a lower alkoxy group, a lower alkoxy group substituted with ahalogen atom, a lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a lower alkylthio group, a lower cycloalkylthiogroup, an arylthio group, heterocyclic thio group, an amino group, alower alkylamino group, a lower cycloalkylamino group, an arylaminogroup, a heterocyclic amino group, an amide of an amino group, an amideof a lower alkylamino group, an amide of a lower cycloalkylamino group,an amide of an arylamino group, an amide of a heterocyclic amino group,a lower alkylcarbonyl group, a lower cycloalkylcarbonyl group, anarylcarbonyl group, a heterocyclic carbonyl group, a carboxy group, anester of a carboxy group, an amide of a carboxy group, a loweralkylsulfonyl group, a lower cycloalkylsulfonyl group, an arylsulfonylgroup, a heterocyclic sulfonyl group, a sulfonic acid group, an ester ofa sulfonic acid group, an amide of a sulfonic acid group, a nitro groupand a cyano group as substituents;

in the case where R⁸ or R⁹ is a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower cycloalkylcarbonyl group, an arylcarbonylgroup, a heterocyclic carbonyl group, a lower cycloalkyloxycarbonylgroup, an aryloxycarbonyl group, a heterocyclic oxycarbonyl group, alower cycloalkylsulfonyl group, an arylsulfonyl group, a heterocyclicsulfonyl group, a lower cycloalkylaminocarbonyl group, anarylaminocarbonyl group or a heterocyclic aminocarbonyl group, the lowercycloalkyl group, aryl group, heterocyclic group, lowercycloalkylcarbonyl group, arylcarbonyl group, heterocyclic carbonylgroup, lower cycloalkyloxycarbonyl group, aryloxycarbonyl group,heterocyclic oxycarbonyl group, lower cycloalkylsulfonyl group,arylsulfonyl group, heterocyclic sulfonyl group, lowercycloalkylaminocarbonyl group, arylaminocarbonyl group or heterocyclicaminocarbonyl group may have one or a plurality of groups selected froma halogen atom, a lower alkyl group, a lower alkyl group substitutedwith a halogen atom, a lower alkyl group substituted with a hydroxygroup, a lower alkenyl group, a lower alkynyl group, a lower cycloalkylgroup, an aryl group, a heterocyclic group, a hydroxy group, an ester ofa hydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith a halogen atom, a lower alkenyloxy group, a lower alkynyloxy group,a lower cycloalkyloxy group, an aryloxy group, a heterocyclic oxy group,a lower alkylthio group, lower cycloalkylthio group, an arylthio group,a heterocyclic thio group, an amino group, a lower alkylamino group, alower cycloalkylamino group, an arylamino group, a heterocyclic aminogroup, an amide of an amino group, an amide of a lower alkylamino group,an amide of a lower cycloalkylamino group, an amide of an arylaminogroup, an amide of a heterocyclic amino group, a lower alkylcarbonylgroup, a lower cycloalkylcarbonyl group, an arylcarbonyl group, aheterocyclic carbonyl group, a carboxy group, an ester of a carboxygroup, an amide of a carboxy group, a lower alkylsulfonyl group, a lowercycloalkylsulfonyl group, an arylsulfonyl group, a heterocyclic sulfonylgroup, a sulfonic acid group, an ester of a sulfonic acid group, anamide of a sulfonic acid group, a nitro group and a cyano group assubstituents;

in the case where R⁷ is NR⁸R⁹, R⁸ and R⁹ may be combined together form a5- or 6-membered nitrogen-containing heterocyclic ring; and/or

(a10) X represents O or S.

That is, in the compounds represented by the general formula (1),preferred examples include compounds that comprises one or a combinationof two or more selected from the above (a1), (a2), (a3), (a4), (a5),(a6), (a7), (a8), (a9) and (a10), and salts thereof.

(b) More preferred examples of the present compound include compounds inwhich the respective groups are groups as defined below and saltsthereof in the compounds represented by the general formula (1) andsalts thereof.

In the general formula (1),

(b1) R¹ represents a halogen atom, a lower alkyl group, a hydroxy group,an ester of a hydroxy group, a lower alkoxy group, a lower alkylthiogroup, an amino group, a lower alkylamino group, an amide of an aminogroup, an amide of a lower alkylamino group, a lower alkylcarbonylgroup, a carboxy group, an ester of a carboxy group, an amide of acarboxy group, a lower alkylsulfonyl group, a nitro group or a cyanogroup;

in the case where R¹ is a lower alkyl group, a lower alkoxy group, alower alkylthio group, a lower alkylamino group, an amide of a loweralkylamino group, a lower alkylcarbonyl group or a lower alkylsulfonylgroup, the lower alkyl group, lower alkoxy group, lower alkylthio group,lower alkylamino group, amide of a lower alkylamino group, loweralkylcarbonyl group or lower alkylsulfonyl group may have one or aplurality of groups selected from a halogen atom, a lower cycloalkylgroup, an aryl group, a heterocyclic group, a hydroxy group, an ester ofa hydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith a halogen atom, a lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a lower alkylthio group, a lower cycloalkylthiogroup, an arylthio group, a heterocyclic thio group, an amino group, alower alkylamino group, a lower cycloalkylamino group, an arylaminogroup, a heterocyclic amino group, an amide of an amino group, an amideof a lower alkylamino group, an amide of a lower cycloalkylamino group,an amide of an arylamino group, an amide of a heterocyclic amino group,a lower alkylcarbonyl group, a lower cycloalkylcarbonyl group, anarylcarbonyl group, a heterocyclic carbonyl group, carboxy group, anester of a carboxy group, an amide of a carboxy group, a loweralkylsulfonyl group, a lower cycloalkylsulfonyl group, an arylsulfonylgroup, a heterocyclic sulfonyl group, a sulfonic acid group, an ester ofa sulfonic acid group, an amide of a sulfonic acid group, a nitro groupand a cyano group as substituents; and/or

(b2) p represents an integer of 0 to 3;

in the case where p is 2 or 3, each R¹ may be the same or different;and/or

(b3) q represents 0; and/or

(b4) R³ represents a hydrogen atom, a lower alkyl group, lower alkenylgroup, a lower alkylcarbonyl group, a lower alkenylcarbonyl group or anarylcarbonyl group;

in the case where R³ is a lower alkyl group, the lower alkyl group mayhave one or a plurality of aryl groups as substituents;

in the case where R³ is an arylcarbonyl group, the arylcarbonyl groupmay have one or a plurality of groups selected from a halogen atom and alower alkyl group as substituents; and/or

(b5) R⁴ and R⁵ may be the same or different and represent a hydrogenatom, a halogen atom, a lower alkyl group, a lower cycloalkyl group,aryl or a heterocyclic group;

in the case where R⁴ or R⁵ is a lower alkyl group, the lower alkyl groupmay have one or a plurality of groups selected from a halogen atom, ahydroxy group, an ester of a hydroxy group, a lower alkoxy group, alower alkoxy group substituted with a halogen atom, a lower alkylthiogroup, an amino group, a lower alkylamino group, an amide of an aminogroup, an amide of a lower alkylamino group, a lower alkylcarbonylgroup, a carboxy group, an ester of a carboxy group, an amide of acarboxy group, a nitro group and a cyano group as substituents;

in the case where R⁴ or R⁵ is a lower cycloalkyl group, aryl orheterocyclic group, the lower cycloalkyl group, aryl or heterocyclicgroup may have one or a plurality of groups selected from a halogenatom, a lower alkyl group, a lower alkyl group substituted with ahalogen atom, a hydroxy group, an ester of a hydroxy group, a loweralkoxy group, a lower alkoxy group substituted with a halogen atom,lower alkylthio group, an amino group, a lower alkylamino group, anamide of an amino group, an amide of a lower alkylamino group, a loweralkylcarbonyl group, a carboxy group, an ester of a carboxy group, anamide of a carboxy group, a lower alkylsulfonyl group, a nitro group anda cyano group as substituents;

R⁴ and R⁵ may be combined together to form a 3- to 8-membered lowercycloalkane ring; and/or

(b6) R⁶ represents a hydrogen atom, a lower alkyl group, a lower alkenylgroup, a lower alkynyl group or a lower cycloalkyl group;

in the case where R⁶ is a lower alkyl group, a lower alkenyl group, alower alkynyl group or a lower cycloalkyl group, the lower alkyl group,lower alkenyl group, lower alkynyl group or lower cycloalkyl group mayhave one or a plurality of groups selected from a halogen atom and anaryl group as substituents; and/or

(b7) A represents a lower alkylene group; and/or

(b8) R⁷ represents OR⁸, NR⁸R⁹ or SR⁸;

R⁸ and R⁹ may be the same or different and represent a hydrogen atom, alower alkyl group, a lower alkenyl group, a lower alkynyl group, a lowercycloalkyl group, an aryl group, a heterocyclic group, a formyl group, alower alkylcarbonyl group, a lower alkenylcarbonyl group, a loweralkynylcarbonyl group, lower cycloalkylcarbonyl group, an arylcarbonylgroup, a heterocyclic carbonyl group, a carboxy group, a loweralkoxycarbonyl group, a lower alkenyloxycarbonyl group, a loweralkynyloxycarbonyl group, a lower cycloalkyloxycarbonyl group, anaryloxycarbonyl group, a heterocyclic oxycarbonyl group, a loweralkylsulfonyl group, a lower alkenylsulfonyl group, a loweralkynylsulfonyl group, a lower cycloalkylsulfonyl group, an arylsulfonylgroup, a heterocyclic sulfonyl group, an aminocarbonyl group, a loweralkylaminocarbonyl group, a lower alkenylaminocarbonyl group, a loweralkynylaminocarbonyl group, a lower cycloalkylaminocarbonyl group, anarylaminocarbonyl group or a heterocyclic aminocarbonyl group;

in the case where R⁸ or R⁹ is a lower alkyl group, a lower alkenylgroup, a lower alkynyl group, a lower alkylcarbonyl group, a loweralkenylcarbonyl group, a lower alkynylcarbonyl group, a loweralkoxycarbonyl group, a lower alkenyloxycarbonyl group, a loweralkynyloxycarbonyl group, a lower alkylsulfonyl group, a loweralkenylsulfonyl group, a lower alkynylsulfonyl group, a loweralkylaminocarbonyl group, a lower alkenylaminocarbonyl group or a loweralkynylaminocarbonyl group, the lower alkyl group, lower alkenyl group,lower alkynyl group, lower alkylcarbonyl group, lower alkenylcarbonylgroup, lower alkynylcarbonyl group, lower alkoxycarbonyl group, loweralkenyloxycarbonyl group, lower alkynyloxycarbonyl group, loweralkylsulfonyl group, lower alkenylsulfonyl group, lower alkynylsulfonylgroup, lower alkylaminocarbonyl group, lower alkenylaminocarbonyl groupor lower alkynylaminocarbonyl group may have one or a plurality ofgroups selected from a halogen atom, a lower cycloalkyl group, an arylgroup, a heterocyclic group, a hydroxy group, an ester of a hydroxygroup, a lower alkoxy group, a lower alkoxy group substituted with ahalogen atom, a lower alkylthio group, an amino group, a loweralkylamino group, an amide of an amino group, an amide of a loweralkylamino group, a lower alkylcarbonyl group, a carboxy group, an esterof a carboxy group, an amide of a carboxy group, a lower alkylsulfonylgroup, a nitro group and a cyano group as substituents;

in the case where R⁸ or R⁹ is a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower cycloalkylcarbonyl group, an arylcarbonylgroup, a heterocyclic carbonyl group, a lower cycloalkyloxycarbonylgroup, an aryloxycarbonyl group, a heterocyclic oxycarbonyl group, alower cycloalkylsulfonyl group, an arylsulfonyl group, a heterocyclicsulfonyl group, a lower cycloalkylaminocarbonyl group, anarylaminocarbonyl group or a heterocyclic aminocarbonyl group, the lowercycloalkyl group, aryl group, heterocyclic group, lowercycloalkylcarbonyl group, arylcarbonyl group, heterocyclic carbonylgroup, lower cycloalkyloxycarbonyl group, aryloxycarbonyl group,heterocyclic oxycarbonyl group, lower cycloalkylsulfonyl group,arylsulfonyl group, heterocyclic sulfonyl group, lowercycloalkylaminocarbonyl group, arylaminocarbonyl group or heterocyclicaminocarbonyl group may have one or a plurality of groups selected froma halogen atom, a lower alkyl group, a lower alkyl group substitutedwith a halogen atom, a lower alkyl group substituted with a hydroxygroup, a lower alkenyl group, a lower alkynyl group, a lower cycloalkylgroup, an aryl group, a heterocyclic group, a hydroxy group, an ester ofa hydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith a halogen atom, a lower alkenyloxy group, a lower alkynyloxy group,a lower alkylthio group, an amino group, a lower alkylamino group, anamide of an amino group, an amide of a lower alkylamino group, a loweralkylcarbonyl group, a carboxy group, an ester of carboxy group, anamide of a carboxy group, a lower alkylsulfonyl group, a nitro group anda cyano group as substituents;

in the case where R⁷ is NR⁸R⁹, R⁸ and R⁹ may be combined together toform a 5- or 6-membered nitrogen-containing heterocyclic ring; and/or

(b9) X represents O.

That is, in the compounds represented by the general formula (1), morepreferred examples include compounds that comprises one or a combinationof two or more selected from the above (b1), (b2), (b3), (b4), (b5),(b6), (b7), (b8) and (b9), and salts thereof.

(c) Further more preferred examples of the present compound includecompounds in which the respective groups are groups as defined below andsalts thereof in the compounds represented by the general formula (1)and salts thereof.

In the general formula (1),

(c1) R¹ represents a halogen atom, a lower alkyl group, a hydroxy group,an ester of a hydroxy group, a lower alkoxy group, a lower alkylthiogroup, an amino group, an amide of an amino group, an amide of a loweralkylamino group, a lower alkylcarbonyl group, a carboxy group, an esterof a carboxy group, a nitro group or a cyano group;

in the case where R¹ is a lower alkyl group or a lower alkoxy group, thelower alkyl group or lower alkoxy group may have one or a plurality ofgroups selected from a halogen atom, a hydroxy group and a lower alkoxygroup as substituents; and/or

(c2) p represents 1, 2 or 3;

in the case where p is 2 or 3, each R¹ may be the same or different;and/or

(c3) q represents 0; and/or

(c4) R³ represents a hydrogen atom; and/or

(c5) R⁴ and R⁵ may be the same or different and represent a lower alkylgroup; and/or

(c6) R⁶ represents a hydrogen atom, a lower alkyl group or a loweralkenyl group; and/or

(c7) A represents a lower alkylene group; and/or

(c8) R⁷ represents OR⁸ or NR⁸R⁹;

R⁸ and R⁹ may be the same or different and represent a hydrogen atom, anaryl group, an arylcarbonyl group or a heterocyclic carbonyl group;

in the case where R⁸ or R⁹ is an aryl group, an arylcarbonyl group or aheterocyclic carbonyl group, the aryl group, arylcarbonyl group orheterocyclic carbonyl group may have one or a plurality of groupsselected from a halogen atom, a lower alkyl group, a lower alkyl groupsubstituted with at least a halogen atom, a lower alkyl groupsubstituted with at least a hydroxy group, a lower alkenyl group, anaryl group, a lower alkoxy group, a lower alkylcarbonyl group, an esterof a carboxy group, a nitro group and a cyano group as substituents;and/or

(c9) X represents O.

That is, in the compounds represented by the general formula (1),further more preferred examples include compounds that comprises one ora combination of two or more selected from the above (c1), (c2), (c3),(c4), (c5), (c6), (c7), (c8) and (c9), and salts thereof.

(d) Further more preferred examples of the present compound includecompounds in which the respective groups are groups as defined below andsalts thereof in the compounds represented by the general formula (1)and salts thereof.

In the general formula (1),

(d1) R¹ represents a halogen atom, a hydroxy group, an ester of ahydroxy group, a lower alkoxy group, an amide of an amino group or anamide of lower alkylamino group; and/or

(d2) p represents 2 or 3, in this case, each R¹ may be the same ordifferent; and/or

(d3) q represents 0; and/or

(d4) R³ represents a hydrogen atom; and/or

(d5) R⁴ and R⁵ may be the same or different and represent a lower alkylgroup; and/or

(d6) R⁶ represents a lower alkyl group; and/or

(d7) A represents a lower alkylene group; and/or

(d8) R⁷ represents OR⁸ or NR⁸R⁹;

R⁸ represents an aryl group, an arylcarbonyl group or a heterocycliccarbonyl group, in this case, the aryl group, arylcarbonyl group orheterocyclic carbonyl group may have one or a plurality of groupsselected from a halogen atom, a lower alkyl group, a lower alkyl groupsubstituted with at least a halogen atom, a lower alkyl groupsubstituted with at least a hydroxy group, a lower alkenyl group, anaryl group, a lower alkoxy group, a lower alkylcarbonyl group, an esterof a carboxy group, a nitro group and a cyano group as substituents;

R⁹ represents a hydrogen atom; and/or

(d9) X represents O.

That is, in the compounds represented by the general formula (1),further more preferred examples include compounds that comprises one ora combination of two or more selected from the above (d1), (d2), (d3),(d4), (d5), (d6), (d7), (d8) and (d9), and salts thereof.

(e) Preferred examples of R¹ in the present compound include compoundsthat satisfy the following requirement and salts thereof.

A compound or a salt thereof wherein in the general formula (1), R¹represents a halogen atom, a hydroxy group, an ester of a hydroxy group,a lower alkoxy group, an amide of an amino group or an amide of a loweralkylamino group; and satisfies the requirement of the above (a), (b)and/or (c).

(f) Preferred examples of R⁴, R⁵ and R⁶ in the present compound includecompounds that satisfy the following requirement and salts thereof.

A compound or a salt thereof wherein in the general formula (1), R⁴, R⁵and R⁶ each represent methyl group, and satisfies the requirement of theabove (a), (b), (c) and/or (d).

(g) Preferred examples of R⁸ in the present compound include compoundsthat satisfy the following requirement and salts thereof.

A compound or a salt thereof wherein in the general formula (1),represents an aryl group, an arylcarbonyl group or a heterocycliccarbonyl group, and the aryl group represents a phenyl group, thearylcarbonyl group represents a phenylcarbonyl group, and/or theheterocyclic carbonyl group represents a thiophenecarbonyl group, andsatisfies the requirement of the above (a), (b), (c) and/or (d).

(h) Preferred examples of A in the present compound include compoundsthat satisfy the following requirement and salts thereof.

A compound or a salt thereof wherein in the general formula (1), Arepresent a methylene group, and satisfies the requirement of the above(a), (b), (c) and/or (d).

(i) Preferred examples of which R¹ is an ester of a hydroxyl group inthe present compound include compounds that satisfy the followingrequirement and salts thereof.

In the R¹ of the general formula (1), the ester of a hydroxy grouprepresents —OCO—R^(a1), in which the R^(a1) represents a hydrogen atom,a lower alkyl group which may have at least a substituent, a loweralkenyl group which may have at least a substituent, a lower alkynylgroup which may have at least a substituent, a lower cycloalkyl groupwhich may have at least a substituent, an aryl group which may have atleast a substituent, a heterocyclic group which may have at least asubstituent, a lower alkoxy group which may have at least a substituent,a lower alkenyloxy group which may have at least substituent, a loweralkynyloxy group which may have at least a substituent, a lowercycloalkyloxy group which may have at least a substituent, an aryloxygroup which may have at least a substituent, a heterocyclic oxy groupwhich may have at least a substituent, an amino group, a loweralkylamino group which may have at least a substituent, a lowercycloalkylamino group which may have at least a substituent, anarylamino group which may have at least a substituent or a heterocyclicamino group which may have at least a substituent,

more preferred examples, the R^(a1) represents a hydrogen atom, a loweralkyl group, a lower alkenyl group, lower cycloalkyl group, an arylgroup, a heterocyclic group, a lower alkoxy group, a lower alkenyloxygroup, a lower cycloalkyloxy group, an aryloxy group, a heterocyclic oxygroup, an amino group, a lower alkylamino group, a lower cycloalkylaminogroup, an arylamino group or a heterocyclic amino group;

in the case where R^(a1) is a lower alkyl group, lower alkenyl group, alower alkoxy group, a lower alkenyloxy group or a lower alkylaminogroup, the lower alkyl group, lower alkenyl group, lower alkoxy group,lower alkenyloxy group or lower alkylamino group may have one or aplurality of groups selected from a halogen atom, an aryl group, aheterocyclic group, a hydroxy group, an ester of a hydroxy group, anamino group, a lower alkylamino group, a carboxy group and an ester of acarboxy group as substituents; and

in the case where R^(a1) is a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a lower cycloalkylamino group, an arylaminogroup or a heterocyclic amino group, the lower cycloalkyl group, arylgroup, heterocyclic group, lower cycloalkyloxy group, aryloxy group,heterocyclic oxy group, lower cycloalkylamino group, arylamino group orheterocyclic amino group may have one or a plurality of groups selectedfrom a halogen atom, a lower alkyl group, a lower alkyl groupsubstituted with at least a halogen atom, a hydroxy group, an ester of ahydroxy group, a lower alkoxy group, a mercapto group, a lower alkylthiogroup, formyl group, a lower alkylcarbonyl group, a carboxy group, anester of a carboxy group, a nitro group and a cyano group assubstituents,

further more preferred examples, the R^(a1) represents a lower alkylgroup, a lower alkenyl group, a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower alkoxy group, an aryloxy group, a loweralkylamino group, a lower cycloalkylamino group, an arylamino group or aheterocyclic amino group;

in the case where R^(a1) is a lower alkyl group, the lower alkyl groupmay have one or a plurality of groups selected from an aryl group and alower alkylamino group as substituents;

in the case where R^(a1) is an aryl group, the aryl group may have oneor a plurality of groups selected from a halogen atom, a lower alkylgroup, a lower alkyl group substituted with at least a halogen atom, anester of a hydroxy group, a lower alkoxy group, a lower alkylthio group,a lower alkylcarbonyl group, an ester of a carboxy group and a nitrogroup as substituents;

in the case where R^(a1) is a heterocyclic group, the heterocyclic groupmay have one or a plurality of groups selected from a halogen atom, alower alkyl group, a hydroxy group and a lower alkoxy group assubstituents;

in the case where R^(a1) is a lower alkylamino group, the loweralkylamino group may have one or a plurality of groups selected from anaryl group, a heterocyclic group and an ester of a carboxy group assubstituents; and

in the case where R^(a1) is an arylamino group, the arylamino group mayhave one or a plurality of groups selected from a halogen atom, a loweralkyl group and a lower alkoxy group as substituents, and satisfies therequirement of the above (a), (b), (c) (d) and/or (e).

(j) Preferred examples of which R¹ is an amide of an amino group in thepresent compound include compounds that satisfy the followingrequirement and salts thereof.

In the R¹ of the general formula (1), the amide of an amino grouprepresents —NHCO—R^(b1), in which the R^(b1) represents a hydrogen atom,a lower alkyl group which may have at least a substituent, a loweralkenyl group which may have at least a substituent, a lower alkynylgroup which may have at least a substituent, a lower cycloalkyl groupwhich may have at least a substituent, an aryl group which may have atleast a substituent, a heterocyclic group which may have at least asubstituent, a lower alkoxy group which may have at least a substituent,a lower alkenyloxy group which may have at least a substituent, a loweralkynyloxy group which may have at least a substituent, a lowercycloalkyloxy group which may have at least a substituent, an aryloxygroup which may have at least a substituent, a heterocyclic oxy groupwhich may have at least a substituent, an amino group, a loweralkylamino group which may have at least substituent, a lowercycloalkylamino group which may have at least a substituent, anarylamino group which may have at least a substituent or a heterocyclicamino group which may have at least a substituent,

more preferred examples, R^(b1) represents a hydrogen atom, a loweralkyl group, a lower alkenyl group, a lower cycloalkyl group, an arylgroup, a heterocyclic group, a lower alkoxy group, a lower alkenyloxygroup, a lower cycloalkyloxy group, an aryloxy group, a heterocyclic oxygroup, an amino group, a lower alkylamino group, a lower cycloalkylaminogroup, an arylamino group or a heterocyclic amino group;

in the case where R^(b1) is a lower alkyl group, a lower alkenyl group,a lower alkoxy group, a lower alkenyloxy group or a lower alkylaminogroup, the lower alkyl group, lower alkenyl group, lower alkoxy group,lower alkenyloxy group or lower alkylamino group may have one or aplurality of groups selected from a halogen atom, an aryl group, aheterocyclic group, a hydroxy group, an ester of a hydroxy group, anamino group, a lower alkylamino group, a carboxy group and an ester of acarboxy group as substituents; and

in the case where R^(b1) is lower cycloalkyl group, an aryl group, aheterocyclic group, a lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a lower cycloalkylamino group, an arylaminogroup or a heterocyclic amino group, the lower cycloalkyl group, arylgroup, heterocyclic group, lower cycloalkyloxy group, aryloxy group,heterocyclic oxy group, lower cycloalkylamino group, arylamino group orheterocyclic amino group may have one or a plurality of groups selectedfrom a halogen atom, a lower alkyl group, a lower alkyl groupsubstituted with at least a halogen atom, a hydroxy group, an ester of ahydroxy group, a lower alkoxy group, a mercapto group, a lower alkylthiogroup, a formyl group, a lower alkylcarbonyl group, a carboxy group, anester of a carboxy group, a nitro group and a cyano group assubstituents,

further more preferred examples, the R^(b1) represents a lower alkylgroup, an aryl group, a heterocyclic group, an aryloxy group, a loweralkylamino group or an arylamino group;

in the case where R^(b1) is a lower alkyl group, the lower alkyl groupmay have one or a plurality of amino groups as substituents;

in the case where R^(b1) is an aryl group, the aryl group may have oneor a plurality of groups selected from a halogen atom, a lower alkylgroup, a lower alkyl group substituted with at least a halogen atom, anester of a hydroxy group, a lower alkoxy group, a lower alkylthio group,a lower alkylcarbonyl group, an ester of a carboxy group and a nitrogroup as substituents;

in the case where R^(b1) is a heterocyclic group, the heterocyclic groupmay have one or a plurality of groups selected from a halogen atom, alower alkyl group, a hydroxy group and a lower alkoxy group assubstituents; and

in the case where R^(b1) is a lower alkylamino group, the loweralkylamino group may have one or a plurality aryl groups assubstituents, and satisfies the requirement of the above (a), (b), (c)(d) and/or (e).

(k) Preferred examples of which R¹ is an amide of a lower alkylaminogroup in the present compound include compounds that satisfy thefollowing requirement and salts thereof.

In the R¹ of the general formula (1), the amide of a lower alkylaminogroup represents —NR^(c1)CO—R^(c2), in which the R^(c1) represents alower alkyl group which may have at least a substituent, and the R^(c2)represents a hydrogen atom, a lower alkyl group which may have at leasta substituent, a lower alkenyl group which may have at least asubstituent, a lower alkynyl group which may have at least asubstituent, a lower cycloalkyl group which may have at least asubstituent, an aryl group which may have at least a substituent, aheterocyclic group which may have at least a substituent, a lower alkoxygroup which may have at least a substituent, a lower alkenyloxy groupwhich may have at least a substituent, a lower alkynyloxy group whichmay have at least a substituent, a lower cycloalkyloxy group which mayhave at least a substituent, an aryloxy group which may have at least asubstituent, a heterocyclic oxy group which may have at least asubstituent, an amino group, a lower alkylamino group which may have atleast a substituent, a lower cycloalkylamino group which may have atleast a substituent, an arylamino group which may have at least asubstituent or a heterocyclic amino group which may have at least asubstituent,

more preferred examples, the R^(c1) represents a lower alkyl group, andthe R^(c2) represents a hydrogen atom, a lower alkyl group, a loweralkenyl group, a lower cycloalkyl group, an aryl group, a heterocyclicgroup, a lower alkoxy group, a lower alkenyloxy group, a lowercycloalkyloxy group, an aryloxy group, a heterocyclic oxy group, anamino group, a lower alkylamino group, lower cycloalkylamino group, anarylamino group or a heterocyclic amino group;

in the case where R^(c2) is a lower alkyl group, a lower alkenyl group,a lower alkoxy group, a lower alkenyloxy group or a lower alkylaminogroup, the lower alkyl group, lower alkenyl group, lower alkoxy group,lower alkenyloxy group or lower alkylamino group may have one or aplurality of groups selected from a halogen atom, an aryl group, aheterocyclic group, a hydroxy group, an ester of a hydroxy group, anamino group, a lower alkylamino group, a carboxy group and an ester of acarboxy group as substituents; and

in the case where R^(c2) is a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a lower cycloalkylamino group, an arylaminogroup or a heterocyclic amino group, the lower cycloalkyl group, arylgroup, heterocyclic group, lower cycloalkyloxy group, aryloxy group,heterocyclic oxy group, lower cycloalkylamino group, arylamino group orheterocyclic amino group may have one or a plurality of groups selectedfrom a halogen atom, a lower alkyl group, a lower alkyl groupsubstituted with at least a halogen atom, a hydroxy group, an ester of ahydroxy group, a lower alkoxy group, a mercapto group, a lower alkylthiogroup, a formyl group, a lower alkylcarbonyl group, a carboxy group, anester of a carboxy group, a nitro group and a cyano group assubstituents,

further more preferred examples, the R^(c1) represents a lower alkylgroup, and the R^(c2) represents a lower alkyl group, an aryl group or aheterocyclic group;

in the case where R^(c2) is a lower alkyl group, the lower alkyl groupmay have one or a plurality of amino groups as substituents;

in the case where R^(c2) is an aryl group, the aryl group may have oneor a plurality of groups selected from a halogen atom, a lower alkylgroup, a lower alkyl group substituted with at least a halogen atom, anester of a hydroxy group, a lower alkoxy group, a lower alkylthio group,a lower alkylcarbonyl group, an ester of a carboxy group and a nitrogroup as substituents;

in the case where R^(c2) is a heterocyclic group, the heterocyclic groupmay have one or a plurality of groups selected from a halogen atom, alower alkyl group, a hydroxy group and a lower alkoxy group assubstituents; and

in the case where R^(c2) is a lower alkylamino group, the loweralkylamino group may have one or a plurality of aryl groups assubstituents, and satisfies the requirement of the above (a), (b), (c)(d) and/or (e).

(l) Particularly preferred specific examples of the present compoundinclude the following compounds and salts thereof. A compound or a saltthereof selected from

-   7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(4-methoxybenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(5-Fluoro-2-methoxyphenyl)-8-(4-methylbenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Fluoro-2-methoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Bromothiophen-2-ylcarbonyloxymethyl)-7-(4-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Fluoro-2-methoxyphenyl)-8-(2-methyl-5-nitrophenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(5-Chloro-2-methoxyphenyl)-8-[2-(2-hydroxyethyl)phenoxymethyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Chloro-2-methylphenoxymethyl)-7-(4-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Fluoro-2-methoxyphenyl)-8-(2-methoxy-5-nitrophenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-quinoxalin-2-one-   8-(2-Allylphenoxymethyl)-7-(4-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Fluoro-2-methoxyphenyl)-8-(2-methoxy-5-methylphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(5-Chloro-2-methoxyphenyl)-8-(5-fluoro-2-methylphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(5-Chloro-2-methoxyphenyl)-8-(2-isopropylphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Fluoro-2-methoxyphenyl)-8-(2-methoxyphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-Benzoyloxymethyl-7-(5-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(5-Fluoro-2-methoxyphenyl)-8-phenoxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(5-Fluoro-2-methoxyphenyl)-8-phenylaminomethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   1-Ethyl-7-(5-fluoro-2-methoxyphenyl)-8-(4-methylbenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one-   1-(Propen-3-yl)-7-(5-fluoro-2-methoxyphenyl)-8-(4-methylbenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(4-methoxybenzoyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(2-methoxy-5-nitrophenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(3-Fluorobenzoyloxymethyl)-7-[2-methoxy-4-(2-methylbenzoyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(2-Chlorophenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methylthiophenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Fluoro-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(5-Chloro-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-5-trifluoromethylphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(6-Fluoro-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-5-nitrophenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(5-Benzoyloxy-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(2-Methoxyphenylaminomethyl)-7-(2-methoxy-5-trifluoromethylphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Amino-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(5-hydroxymethyl-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(4-hydroxy-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Hydroxy-2-methoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(2-methylbenzoyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[4-(furan-3-ylcarbonyloxy)-2-methoxyphenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(pyridin-4-ylcarbonylamino)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[4-(2-Chlorobenzoylamino)-2-methoxyphenyl]-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(4-methoxybenzoyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Acryloyloxy-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-4-methoxycarbonyloxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-4-phenoxycarbonyloxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-4-phenoxycarbonylaminophenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(3-methoxycarbonylbenzoyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[4-(2-Acetoxybenzoyloxy)-2-methoxyphenyl]-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(2-methylthiobenzoyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(6-methylpyridin-3-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(oxazol-4-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[4-(3-Acetylbenzoyloxy)-2-methoxyphenyl]-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[4-(3-Chlorothiophen-2-ylcarbonyloxy)-2-methoxyphenyl]-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[2-Methoxy-4-(2-methylthiobenzoyloxy)phenyl]-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[4-(N-Acetyl-N-methylamino)-2-methoxyphenyl]-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(pyridin-3-ylaminocarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(2-Methoxy-4-phenylaminocarbonyloxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Dimethylaminocarbonyloxy-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Hydroxy-2-methoxyphenyl)-8-(2-methoxyphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Butyryloxy-2-methoxyphenyl)-8-(2-methoxyphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[2-Methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-8-(2-methoxyphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(2-Methoxyphenylaminomethyl)-7-[2-methoxy-4-(thiazol-4-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-[N-(5-Fluoro-2-methylphenyl)-N-(9-fluorenylmethoxycarbonyl)aminomethyl]-7-(4-hydroxy-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(2-methoxy-5-nitrophenoxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methylphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Benzoyloxy-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-(4-Benzoyloxy-2-methoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[4-(Furan-2-ylcarbonyloxy)-2-methoxyphenyl]-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[2-Methoxy-4-(2-methoxybenzoyloxy)phenyl]-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[2-Methoxy-4-(3-methoxycarbonylbenzoyloxy)phenyl]-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[2-Methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[4-(3-Benzylureido)-2-methoxyphenyl]-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(3-phenylureido)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(2-Methoxyphenylaminomethyl)-7-[2-methoxy-4-(pyridine-3-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   7-[2-Methoxy-4-(2-methoxybenzoyloxy)phenyl]-8-(2-methoxyphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one-   8-(2-Methoxyphenylaminomethyl)-7-[2-methoxy-4-(thiophen-3-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one,    and-   7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(2-methoxyphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one

The present compound can be synthesized according to the followingprocedures. The individual concrete preparation procedures are explainedin details in the following examples, [preparation examples]. Theseexamples are intended to make the present invention more clearlyunderstandable, and do not limit the scope of the present invention. TheHal shown in the following synthetic routes represents a halogen atom,MOM represents methoxymethyl group and Fmoc represents9-fluorenylmethoxycarbonyl group.

The present compound (I)-(a) (the compound that A is methylene group, Xis O in the general formula (1)) can be synthesized according to thesynthetic route 1. Namely, the compound (I)-(a) can be given by thereaction of the present compound (I)-(b) (the compound that A ismethylene group, X is O, R⁶ is H in the general formula (1)) with acorresponding halide (II) in an organic solvent such asN,N-dimethylformamide (hereinafter referred to as DMF), tetrahydrofuran(hereinafter referred to as THF), 1,4-dioxane, methylene dichloride inthe presence of a base such as cesium carbonate, potassium carbonate at0° C. to 50° C. for 1 hour to 24 hours.

The present compound (I)-(b) (the compound that A is methylene group, Xis O, R⁶ is H, R⁷ is OR⁸, NR⁸R⁹ or SR⁸ in the general formula (1)) canbe synthesized according to the synthetic route 2. Namely, the compound(I)-(b) can be given by the reaction of the compound (III) with acorresponding alcohol, carboxylic acid, phenol, amine, thiol, thiophenoland the like (IV) in an organic solvent such as DMF, THF, ethanol in thepresence of a base such as potassium carbonate, sodium hydride at 0° C.to 100° C. for 1 hour to 48 hours.

The present compound (I)-(c) (the compound that A is methylene group, Xis O, R⁷ is OR⁸ in the general formula (1)) can be synthesized accordingto the synthetic route 3. Namely, the compound (I)-(c) can be given bythe reaction of the compound (V) with a corresponding halide (VI) in anorganic solvent such as DMF, THF, methylene dichloride in the presenceof a base such as triethylamine, potassium carbonate at 0° C. to 50° C.for 1 hour to 48 hours.

The compound (III) and (V) can be synthesized according to the syntheticroute 4. Namely, the compound (IX) can be given by the reaction of thecompound (VII) with a corresponding boronic acid or its ester (VIII) ina solvent such as DMF, 1,4-dioxane, ethanol, toluene, water and in thepresence of a base such as cesium carbonate, sodium carbonate, sodiumhydrogen carbonate, tripotassium phosphate and a catalyst such, asbis(triphenylphosphine)palladium (II)dichloride,tetrakis(triphenylphosphine)palladium (0) at 50° C. to 120° C. for 1hour to 48 hours. The compound (V) can be given by the treatment of thecompound (IX) in an organic solvent such as diethylether, THF in thepresence of a reductive agent such as lithium aluminium hydride at −30°C. to room temperature for 1 hour to 24 hours. The compound (III) can begiven by the treatment of the compound (V) with methanesulfonyl chloridein an organic solvent such as methylene dichloride, THF in the presenceof base such as triethylamine, diisopropylethylamine (hereinafterreferred to as DIEA) at 0° C. to room temperature for 30 minutes to 12hours.

The compound (VII) can be synthesized according to the synthetic route5. Namely, the compound (XI) can be given by the treatment of thecompound (X) in an organic solvent such as methanol, ethanol, DMF in thepresence of a reductive agent such as tin(II) chloride, ferric(II)chloride at 50° C. to 120° C. for 1 hour to 12 hours. The compound (XII)can be given by the treatment of the compound (XI) with an acetylationagent such as acetyl chloride, acetic anhydride in an, organic solventsuch as methylene dichloride, THF in the presence of a base such astriethylamine, DIEA at 0° C. to 50° C. for 1 hour to 12 hours. Thecompound (XIII) can be given by the treatment of the compound (XII) withnitric acid in a solvent such as water in the presence of an acid suchas sulfuric acid at −20° C. to room temperature for 30 minutes to 12hours. The compound (XIV) can be given by the treatment of the compound(XIII) in an organic solvent such as methanol in the presence of an acidsuch as boron trifluoride ether complex at 50° C. to the temperatureunder reflux for 1 hour to 12 hours. The compound (XVI) can be given bythe reaction of the compound (XIV) with a corresponding halide (XV) inthe presence of a base such as cesium carbonate, potassium carbonate at50° C. to 120° C. for 1 hour to 120 hours. The compound (VII) can begiven by the treatment of the compound (XVI) in an organic solvent suchas methanol, ethanol, DMF in the presence of reductive agent such astin(II) chloride, ferric(II) chloride at 50° C. to 120° C. for 1 hour to12 hours.

The present compound (I)-(a) (the compound that A is methylene group, Xis O in the general formula (1)) can be also synthesized according tothe synthetic route 6. Namely, the compound (I)-(a) can be given by thereaction of the compound (XVII) with a corresponding boronic acid or itsester (VIII) in a solvent such as DMF, 1,4-dioxane, ethanol, toluene,water and in the presence of a base such as cesium carbonate, sodiumcarbonate, sodium hydrogen carbonate, tripotassium phosphate and acatalyst such as bis(triphenylphosphine)palladium(II)dichloride,tetrakis(triphenylphosphine)palladium (0) at 50° C. to 120° C. for 1hour to 48 hours.

Moreover, the present compound (I)-(a) (the compound that A is methylenegroup, X is O in the general formula (1)) can be also synthesizedaccording to the synthetic route 7. Namely, the compound (I)-(a) can begiven by the reaction of the compound (XVIII) with a correspondinghalide (XIX) in a solvent such as DMF, 1,4-dioxane, ethanol, toluene,water and in the presence of a base such as cesium carbonate, sodiumcarbonate, sodium hydrogen carbonate, tripotassium phosphate and acatalyst such as bis(triphenylphosphine)palladium(II)dichloride,tetrakis(triphenylphosphine)palladium (0) at 50° C. to 120° C. for 1hour to 48 hours.

The compound (XVII) and (XVIII) can be synthesized according to thesynthetic route 8. Namely, the compound (XX) can be given by thetreatment of the compound (VII) in an organic solvent such asdiethylether, THF in the presence of a reductive agent such as lithiumaluminium hydride at 0° C. to 50° C. for 1 hour to 24 hours. Thecompound (XXI) can be given by the reaction of the compound (XX) with acorresponding halide (II) in an organic solvent such as DMF, THF,1,4-dioxane, methylene dichloride in the presence of a base such ascesium carbonate, potassium carbonate at 0° C. to 50° C. for 1 hour to24 hours. The compound (XXII) can be given by the treatment of thecompound (XXI) with methanesulfonyl chloride in an organic solvent suchas methylene dichloride, THF in the presence of base such astriethylamine, DIEA at 0° C. to room temperature for 30 minutes to 12hours. The compound (XVII) can be given by the reaction of the compound(XXII) with a corresponding alcohol, carboxylic acid, phenol, amine,thiol, thiophenol (IV) in an organic solvent such as DMF, THF, ethanolin the presence of a base such as potassium carbonate, sodium hydride at0° C. to 100° C. for 1 hour to 48 hours. The compound (XVIII) can begiven by the reaction of the compound (XVII) with a correspondingdiboron (XXIII) or borane (XXIV) in a solvent such as dimethylsulfoxide,DMF, 1,4-dioxane in the presence of a base such as potassium acetate,triethylamine and a catalyst such as[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride,bis(triphenylphosphine)-palladium(II)dichloride at 50° C. to 120° C. for10 minutes to 48 hours.

The present compound (I)-(d) (the compound that A is methylene group, Xis O, one of R¹ is OR¹⁰, R¹⁰ is a lower alkyl group which may have atleast a substituent, a lower alkylcarbonyl group which may have at leasta substituent, an arylcarbonyl group which may have at least asubstituent, a heterocyclic carbonyl group which may have at least asubstituent, a lower alkoxycarbonyl group which may have at least asubstituent or an aryloxycarbonyl group which may have at least asubstituent, and the like in the general formula (1)) can be synthesizedaccording to the synthetic route 9. Namely, the compound (I)-(d) can begiven by the reaction of the present compound (I)-(e) (the compound thatA is methylene group, X is O, one of R¹ is OH in the general formula(1)) with a corresponding halide (XXV) in an organic solvent such asTHF, methylene dichloride, DMF in the presence of a base such astriethylamine, DIEA, potassium carbonate at 0° C. to 100° C. for 1 hourto 24 hours.

The present compound (I)-(f) (the compound that A is methylene group, Xis O, one of the R¹ is OCOR¹¹, R¹¹ is a lower alkyl group which may haveat least a substituent, an aryl group which may have at least asubstituent or a heterocyclic group which may have at least asubstituent, and the like in the general formula (1)) can be synthesizedaccording to the synthetic route 10. Namely, the compound (I)-(f) can begiven by the reaction of the present compound (I)-(e) (the compound thatA is methylene group, X is O, one of R¹ is OH in the general formula(1)) with a corresponding carboxylic acid (XXVI) in an organic solventsuch as DMF, methylene dichloride in the presence of a condensationagent such as N,N′-dicyclohexylcarbodiimide (hereinafter referred to asDCC), O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate (hereinafter referred to as HATU) and a basesuch as DIEA at room temperature to 50° C. for 1 hour to 3 days.

The present compound (I)-(g) (the compound that A is methylene group, Xis O, one of the R¹ is OCONR¹²R¹³, R¹² and R¹³ may be the same ordifferent and are a lower alkyl group which may have at least asubstituent, an aryl group which may have at least a substituent, andthe like in the general formula (1)) can be synthesized according to thesynthetic route 11. Namely, the compound (I)-(g) can be given by thereaction of the present compound (I)-(e) (the compound that A ismethylene group, X is O, one of the R¹ is OH in the general formula (1))with 1,1′-carbonyldiimidazole (hereinafter referred to as CDI) in anorganic solvent such as methylene dichloride, THF at room temperature to50° C. for 30 minutes to 12 hours followed by the reaction with acorresponding amine (XXVII).

The present compound (I)-(e) (the compound that A is methylene group, Xis O, one of the R¹ is OH in the general formula (1)) can be synthesizedaccording to the synthetic route 12. Namely, the present compound(I)-(h) can be given by the reaction of the compound (XVII) with acorresponding boronic acid or its ester (XXVIII) in a solvent such asDMF, 1,4-dioxane, ethanol, toluene, water in the presence of a base suchas cesium carbonate, sodium carbonate, sodium hydrogen carbonate,tripotassium phosphate and a catalyst such asbis(triphenylphosphine)palladium (II)dichloride,tetrakis(triphenylphosphine)palladium (0) at 50° C. to 120° C. for 1hour to 48 hours. The compound (I)-(e) can be given by the treatment ofthe compound (I)-(h) in an organic solvent such as 1,4-dioxane,methylene dichloride in the presence of an acid such as hydrogenchloride, trifluoroacetic acid at 0° C. to 50° C. for 1 hour to 24hours.

Further, the present compound (I)-(e) (the compound that A is methylenegroup, X is O, one of the R¹ is OH in the general formula (1)) can bealso synthesized according to the synthetic route 13. Namely, thecompound (XXIX) can be given by the reaction of the compound (VII) witha corresponding boronic acid or its ester (XXVIII) in a solvent such asDMF, 1,4-dioxane, ethanol, toluene, water in the presence of a base suchas cesium carbonate, sodium carbonate, sodium hydrogen carbonate,tripotassium phosphate and a catalyst such asbis(triphenylphosphine)palladium(II)dichloride,tetrakis(triphenylphosphine)palladium (0) at 50° C. to 120° C. for 1hour to 48 hours. The compound (XXX) can be given by the treatment ofthe compound (XXIX) in an organic solvent such as diethylether, THF inthe presence of a reductive agent such as lithium aluminium hydride at−30° C. to room temperature for 1 hour to 24 hours. The compound (XXXI)can be given by the treatment of the compound (XXX) with methanesulfonylchloride in an organic solvent such as methylene dichloride, THF in thepresence of a base such as triethylamine, DIEA at 0° C. to roomtemperature for 30 minutes to 12 hours. The present compound (I)-(i) canbe given by the reaction of the compound (XXXI) with a correspondingalcohol, carboxylic acid, phenol, amine, thiol, thiophenol and the like(IV) in an organic solvent such as DMF, THF, ethanol in the presence ofa base such as potassium carbonate, sodium hydride at 0° C. to 100° C.for 1 hour to 48 hours. The present compound (I)-(h) can be given by thereaction of the compound (I)-(i) with a corresponding halide (II) in anorganic solvent such as DMF, THF, 1,4-dioxane, methylene dichloride inthe presence of a base such as cesium carbonate, potassium carbonate at0° C. to 50° C. for 1 hour to 24 hours. The compound (I)-(e) can begiven by the treatment of the compound (I)-(h) in an organic solventsuch as 1,4-dioxane, methylene dichloride in the presence of an acidsuch as hydrogen chloride, trifluoroacetic acid at 0° C. to 50° C. for 1hour to 24 hours.

The present compound (I)-(j) (the compound that A is methylene group, Xis O, one of the R¹ is OR¹⁰, R⁷ is NHR⁸, R¹⁰ is a lower alkyl groupwhich may have at least a substituent, a lower alkylcarbonyl group whichmay have at least a substituent, an arylcarbonyl group which may have atleast substituent, a heterocyclic carbonyl group which may have at leasta substituent, a lower alkoxycarbonyl group which may have at least asubstituent, an aryloxycarbonyl group which may have at least asubstituent, and the like in the general formula (1)), the presentcompound (I)-(k) (the compound that A is methylene group, X is O, one ofthe R¹ is OCOR¹¹, R⁷ is NHR⁸, R¹¹ is a lower alkyl group which may haveat least a substituent, an aryl group which may have at least asubstituent, a heterocyclic group which may have at least a substituent,and the like in the general formula (1)) and the present compound(I)-(1) (the compound that A is methylene group, X is O, one of the R¹is OCONR¹²R¹³, R⁷ is NHR⁸, R¹² and R¹³ may be the same or different andare a lower alkyl group which may have at least a substituent, an arylgroup which may have at least a substituent, and the like in the generalformula (1)) can be synthesized according to the synthetic route 14.Namely, the compound (I)-(j), (I)-(k) and (I)-(l) can be given by thereaction of the present compound (I)-(m) (the compound that A ismethylene group, X is O, one of the R¹ is OH, R⁷ is NR⁸(Fmoc) in thegeneral formula (1)) with a corresponding halide (XXV), a carboxylicacid (XXVI) or an amine (XXVII) according to the method of syntheticroute 9, 10 or 11 respectively, followed by the treatment in an organicsolvent such as DMF, methylene dichloride in the presence of a base suchas piperidine at 0° C. to 50° C. for 5 minutes to 24 hours.

The present compound (I)-(m) (the compound that A is methylene group, Xis O, one of the R¹ is OH, R⁷ is NR⁸(Fmoc) in the general formula (1))can be synthesized according to the synthetic route 15. Namely, thecompound (XXXIII) can be given by the reaction of the compound (XXII)with a corresponding amine (XXXII) in an organic solvent such as DMF,THF, ethanol in the presence of a base such as potassium carbonate,sodium hydride at 0° C. to 100° C. for 1 hour to 48 hours. The presentcompound (I)-(o) can be given by the reaction of the compound (XXXIII)with a corresponding boronic acid or its ester (XXVIII) in a solventsuch as DMF, 1,4-dioxane, ethanol, toluene, water in the presence of abase such as cesium carbonate, sodium carbonate, sodium hydrogencarbonate, tripotassium phosphate and a catalyst such asbis(triphenylphosphine)palladium(II)dichloride,tetrakis(triphenylphosphine)palladium (0) at 50° C. to 120° C. for 1hour to 48 hours. The present compound (I)-(n) can be given by thereaction of the compound (I)-(o) with 9-fluorenylmethoxycarbonylchloride in a solvent such as 1,4-dioxane, water in the presence of abase such as sodium hydrogen carbonate at 0° C. to 50° C. for 1 hour to24 hours. The compound (I)-(m) can be given by the treatment of thecompound (I)-(n) in an organic solvent such as 1,4-dioxane, methylenedichloride in the presence of an acid such as hydrogen chloride,trifluoroacetic acid at 0° C. to 50° C. for 1 hour to 24 hours.

The present compound (I)-(p) (the compound that A is methylene group, Xis O, one of the R¹ is OR¹⁰, R⁷ is OR⁸, R¹⁰ is a lower alkyl group whichmay have at least a substituent, a lower alkylcarbonyl group which mayhave at least a substituent, an arylcarbonyl group which may have atleast a substituent, a heterocyclic carbonyl group which may have atleast a substituent, a lower alkoxycarbonyl group which may have atleast a substituent, an aryloxycarbonyl group which may have at least asubstituent, and the like in the general formula (1)) can be synthesizedaccording to the synthetic route 16. Namely, the compound (XXXIV) can begiven by the treatment of the compound (XXX) in an organic solvent suchas 1,4-dioxane, methylene dichloride in the presence of an acid such ashydrogen chloride, trifluoroacetic acid at 0° C. to 50° C. for 1 hour to24 hours. The compound (XXXV) can be given by the reaction of thecompound (XXXIV) with a corresponding halide (XXV) in an organic solventsuch as THF, methylene dichloride, DMF in the presence of a base such astriethylamine, DIEA, potassium carbonate at 0° C. to 100° C. for 1 hourto 24 hours. The compound (I)-(q) can be given by the reaction of thecompound (XXXV) with a corresponding halide (VI) in an organic solventsuch as DMF, THF, methylene dichloride in the presence of a base such astriethylamine, potassium carbonate at 0° C. to 50° C. for 1 hour to 48hours. The compound (I)-(p) can be given by the reaction of the compound(I)-(q) with a corresponding halide (II) in an organic solvent such asDMF, THF, 1,4-dioxane, methylene dichloride in the presence of a basesuch as cesium carbonate, potassium carbonate at 0° C. to 50° C. for 1hour to 24 hours.

The present invention also relates to a method of preventing or treatinga glucocorticoid receptor-related disease, for example, metabolicdisorders such as diabetes and obesity, inflammatory diseases such asarthritis, enteritis and chronic obstructive pulmonary diseases,autoimmune diseases such as connective tissue diseases, allergicdiseases such as asthma, atopic dermatitis, allergic rhinitis andconjunctivitis, central nervous system diseases such as psychiatricdisorders, Alzheimer's disease and drug use disorders, cardiovasculardiseases such as hypertension, hypercalcemia, hyperinsulinemia andhyperlipidemia, homeostasis-related diseases causing an abnormality ofneuro-immune-endocrine balance, glaucoma, comprising administering to apatient a therapeutically effective amount of the present compound or asalt thereof.

In order to find the usefulness of the present compound as apharmaceutical, by using glucocorticoid receptor competitor assay kit, aglucocorticoid receptor competitor assay was carried out by fluorescencepolarization method. As a result, the present compound showed anexcellent glucocorticoid receptor binding activity. Incidentally, theglucocorticoid receptor is associated with the occurrence of variousdiseases as described above, therefore, the present compound having anexcellent binding activity to the glucocorticoid receptor is useful as aglucocorticoid receptor modulator.

A detailed explanation of this matter will be described in the sectionof “Pharmacological Test” in Examples described below.

The present compound can be administered either orally or parenterally.Examples of the dosage form include a tablet, a capsule, a granule, apowder, an injection, an eye drop and the like. Such preparation can beprepared using a commonly used technique.

For example, an oral preparation such as a tablet, a capsule, a granuleor a powder can be prepared by optionally adding a necessary amount ofan excipient such as lactose, mannitol, starch, crystalline cellulose,light silicic anhydride, calcium carbonate or calcium hydrogenphosphate; a lubricant such as stearic acid, magnesium stearate or talc;a binder such as starch, hydroxypropyl cellulose, hydroxypropylmethylcellulose or polyvinylpyrrolidone; a disintegrant such as carboxymethylcellulose, low-substituted hydroxypropylmethyl cellulose or calciumcitrate; a coating agent such as hydroxypropylmethyl cellulose, macrogolor a silicone resin; a stabilizer such as ethyl p-hydroxybenzoate orbenzyl alcohol; a corrigent such as a sweetener, a sour agent or aflavor, or the like.

A parenteral preparation such as an injection or an eye drop can beprepared by optionally adding a necessary amount of a tonicity agentsuch as sodium chloride, concentrated glycerin, propylene glycol,polyethylene glycol, potassium chloride, sorbitol or mannitol; a buffersuch as sodium phosphate, sodium hydrogen phosphate, sodium acetate,citric acid, glacial acetic acid or trometamol; a surfactant such aspolyoxyethylene sorbitan monoolate, polyoxy 40 stearate orpolyoxyethylene hydrogenated castor oil 60; a stabilizer such as sodiumcitrate or sodium edetate; a preservative such as benzalkonium chloride,paraben, benzothonium chloride, p-hydroxybenzoate ester, sodium benzoateor chlorobutanol; a pH adjusting agent such as hydrochloric acid, citricacid, phosphoric acid, glacial acetic acid, sodium hydroxide, sodiumcarbonate or sodium hydrogen carbonate; a soothing agent such as benzylalcohol, or the like.

The dose of the present compound can be appropriately selected dependingon the symptoms, age, dosage form or the like. For example, in the caseof an oral preparation, it can be administered in an amount of generally0.01 to 1000 mg, preferably 1 to 100 mg per day in a single dose orseveral divided doses. Further, in the case of an eye drop, apreparation containing the present compound at a concentration ofgenerally 0.0001% to 10% (w/v), preferably 0.01% to 5% (w/v) can beadministered in a single dose or several divided doses.

Hereinafter, Production Examples of the present compound, PreparationExamples and results of Pharmacological Test will be described. However,these examples are described for the purpose of understanding thepresent invention better and are not meant to limit the scope of thepresent invention.

Fmoc in the chemical structure in Production Examples represents9-fluorenylmethoxycarbonyl group.

Production Example Reference Example 17-Bromo-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 1) Methyl 5-amino-2-bromobenzoate (ReferenceCompound No. 1-(1))

Methyl 2-bromo-5-nitrobenzoate (25.3 g, 97.3 mmol) was dissolved inanhydrous methanol (500 mL), Tin (II) chloride (93.3 g, 487 mmol) wasadded thereto, and then the reaction mixture was refluxed for 2 hours.The reaction mixture was cooled down, ethyl acetate (500 mL) and water(100 mL) were added thereto, the mixture was neutralized with 4N aqueoussodium hydroxide solution, and then filtered on celite. The filtrate wasconcentrated under reduced pressure, ethyl acetate (200 mL) was addedthereto, and then the mixture was washed with saturated aqueous sodiumhydrogen carbonate solution (200 mL, 2 times), water (200 mL), andsaturated brine (200 mL) successively. The organic layer was dried overanhydrous magnesium sulfate and the solvent was removed under reducedpressure to give the titled reference compound (21.0 g) as a pale yellowoil. (Yield 94%)

¹H-NMR (400 MHz, DMSO-d₆) δ 3.80 (s, 3H), 5.55 (s, 2H), 6.63 (dd, J =8.8, 2.8 Hz, 1H), 6.94 (d, J = 2.8 Hz, 1H), 7.29 (d, J = 8.8 Hz, 1H)

Methyl 5-acetylamino-2-bromobenzoate (Reference Compound No. 1-(2))

Methyl 5-amino-2-bromobenzoate (Reference Compound No. 1-(1), 21.0 g,91.2 mmol) was dissolved in anhydrous dichloromethane (450 mL),triethylamine (19.0 mL, 137 mmol) and acetyl chloride (13.0 mL, 182mmol) were added dropwise over 30 minutes successively, and then themixture was stirred at 0° C. for 2 hours. The reaction mixture waswashed with water (200 mL, 2 times), saturated aqueous sodium hydrogencarbonate solution (200 mL, 2 times), and saturated brine (200 mL)successively, dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. The obtained residue wasfiltered with hexane-ethyl acetate (20:1) to give the titled referencecompound (24.2 g) as a pale yellow solid. (Yield 98%)

¹H-NMR (400 MHz, DMSO-d₆) δ 2.06 (s, 3H), 3.86 (s, 3H), 7.63-7.66 (m,2H), 8.07 (s, 1H), 10.25 (s, 1H)

Methyl 3-acetylamino-6-bromo-2-nitrobenzoate (Reference Compound No.1-(3))

To conc. sulfuric acid (150 mL), methyl 5-acetylamino-2-bromobenzoate(Reference Compound No. 1-(2), 18.5 g, 68.1 mmol) was added at 0° C.portionwise, and conc. nitric acid (150 mL) was added dropwise theretoover 1 hour. The reaction mixture was stirred for 30 minutes, pouredinto iced water (1 L), and then extracted with ethyl acetate (500 mL, 2times). The organic layer was washed with water (1 L, 2 times),saturated aqueous sodium hydrogen carbonate solution (1 L), andsaturated brine (1 L) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled reference compound (13.4 g) asa yellow solid. (Yield 62%)

¹H-NMR (400 MHz, DMSO-d₆) δ 2 .05 (s, 3H), 3.87 (s, 3H), 7.55 (d, J =8.8 Hz, 1H), 8.02 (d, J = 8.8 Hz, 1H), 10.48 (s, 1H)

Methyl 3-amino-6-bromo-2-nitrobenzoate (Reference Compound No. 1-(4))

Methyl 3-acetylamino-6-bromo-2-nitrobenzoate (Reference Compound No.1-(3), 13.4 g, 42.2 mmol) was dissolved in methanol (240 mL), borontrifluoride diethyl etherate complex (24.0 mL, 190 mmol) was addedthereto, and then the mixture was refluxed for 2.5 hours. After thereaction mixture was neutralized with sodium hydrogen carbonate (48 g),the mixture was concentrated under reduced pressure. After ethyl acetate(500 mL) and water (700 mL) were added thereto and the mixture waspartitioned, the ethyl acetate layer was washed with water (700 mL) andsaturated brine (700 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure to givethe titled reference compound (11.6 g) as an orange solid. (Yield 100%)

¹H-NMR (500 MHz, CDCl₃) δ 3.98 (s, 3H), 6.15 (br s, 2H), 6.78 (d, J =9.2 Hz, 1H), 7.48 (d, J = 9.2 Hz, 1H)

Methyl 6-bromo-3-[(2-ethoxycarbonyl)propan-2-yl]amino-2-nitrobenzoate(Reference Compound No. 1-(5))

The mixture of methyl 3-amino-6-bromo-2-nitrobenzoate (ReferenceCompound No. 1-(4), 11.6 g, 42.0 mmol), ethyl 2-bromoisobutyrate (60.4mL, 412 mmol), potassium iodide (7.76 g, 46.2 mmol) and cesium carbonate(56.1 g, 172 mmol) was stirred at 85° C. for 4 days. After the mixturewas cooled down, ethyl acetate (500 mL) and water (500 mL) were addedthereto, the mixture was partitioned, and then the water layer wasextracted with ethyl acetate (300 mL). The organic layer was combined,washed with water (1 L, 2 times) and saturated brine (1 L) successively,dried over anhydrous magnesium sulfate, and then the solvent was removedunder reduced pressure. The obtained residue was purified by silica gelcolumn chromatography (hexane-ethyl acetate) to give the titledreference compound (5.08 g) as an orange oil. (Yield 31%)

¹H-NMR (400 MHz, CDCl₃) δ 1.22 (t, J = 7.1 Hz, 3H), 1.65 (s, 6H), 3.98(s, 3H), 4.20 (d, J = 7.1 Hz, 2H), 6.56 (d, J = 9.4 Hz, 1H), 7.49 (d, J= 9.4 Hz, 1H), 8.31 (s, 1H)

7-Bromo-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 1)

Methyl 6-bromo-3-[(2-ethoxycarbonyl)propan-2-yl]amino-2-nitrobenzoate(Reference Compound No. 1-(5), 105 mg, 0.26 mmol) was dissolved inanhydrous ethanol (4.5 mL), tin (II) chloride (247 mg, 1.30 mmol) wasadded thereto, and then the reaction mixture was refluxed for 5 hours.After the reaction mixture was cooled down, ethyl acetate (25 mL) wasadded thereto, the mixture was neutralized with aqueous sodium hydrogencarbonate solution, and then filtered on celite. After the filtrate waspartitioned, the water layer was extracted with ethyl acetate (10 mL, 2times), the combined organic layer was washed with water (50 mL, 2times) and saturated brine (50 mL) successively, dried over anhydrousmagnesium sulfate, and then the solvent was removed under reducedpressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled referencecompound (56.3 mg) as a pale yellow solid. (Yield 70%)

¹H-NMR (400 MHz, CDCl₃) δ 1.39 (s, 6H), 3.86 (s, 1H), 3.98 (s, 3H), 6.62(d, J = 8.5 Hz, 1H), 7.13 (d, J = 8.5 Hz, 1H), 8.89 (s, 1H)

Reference Example 28-Methoxycarbonyl-7-(2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 2-1)

A mixture of7-bromo-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 1, 203 mg, 0.64 mmol), 2-methoxyphenylboronicacid (196 mg, 1.28 mmol), cessium carbonate (629 mg, 1.92 mmol) andbis(triphenylphosphine)palladium dichloride (II) (45.8 mg, 0.06 mmol)was suspended with anhydrous N,N-dimethylformamide (3 ml) and stirred at80° C. for days. After the mixture was cooled down, ethyl acetate (30mL) and water (30 mL) were added thereto and the mixture waspartitioned. The organic layer was washed with water (30 mL) andsaturated brine (30 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled reference compound (116 mg) asa pale yellow amorphous product. (Yield 31%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.56 (s, 6H), 3.50 (s, 3H), 3.72 (s, 3H),3.84 (s, 1H), 6.81 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 8.1 Hz, 1H), 6.86(dd, J = 7.7, 0.9 Hz, 1H), 7.01 (td, J =7.7, 0.9 Hz, 1H), 7.22 (dd, J =7.7, 1.7 Hz, 1H), 7.28 (td, J = 7.7, 1.7 Hz, 1H), 9.56 (s, 1H)Using any compounds among Reference Compounds No. 1, 18-3, 18-5 andavailable compounds, the following Reference Compounds (No. 2-2˜2-5)were obtained by a method similar to that of Reference Compound No. 2-1.

7-(4-Fluoro-2-methoxyphenyl)-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 2-2)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.27 (s, 6H), 3.50 (s, 3H), 3.65 (s, 3H),6.41 (s, 1H), 6.74 (d, J = 8.2 Hz, 1H), 6.78 (td, J = 8.5, 2.4 Hz, 1H),6.87 (dd, J = 11.3, 2.4 Hz, 1H), 6.89 (d, J = 8.2 Hz, 1H), 7.14 (dd, J =8.5, 7.0 Hz, 1H), 9.48 (s, 1H)7-(5-Fluoro-2-methoxyphenyl)-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound 2-3)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.27 (s, 6H), 3.50 (s, 3H), 3.61 (s, 3H),6.46 (s, 1H), 6.78 (d, J = 8.2 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 6.94(dd, J = 8.8, 4.7 Hz, 1H), 7.00 (dd, J = 9.3, 3.2 Hz, 1H), 7.08 (td, J =8.8, 3.2 Hz, 1H), 9.49 (s, 1H)8-Methoxycarbonyl-7-(2-methoxy-4-methoxymethoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No.2-4)  

¹H-NMR (500 MHz, CDCl₃) δ 1.42 (br s, 6H), 3.52 (s, 3H), 3.54 (s, 3H),3.70 (s, 3H), 3.81 (br s, 1H), 5.21 (s, 2H), 6.57 (d, J = 2.1 Hz, 1H),6.69 (dd, J = 8.2, 2.1 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 6.82 (d, J =8.2 Hz, 1H), 7.12 (d, J = 8.2 Hz, 1H), 9.51 (s, 1H)7-(4-Benzoyloxy-2-methoxyphenyl)-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No.2-5)  

¹H-NHR (400 MHz, CDCl₃) δ 1.41 (br s, 3H), 1.48 (br s, 3H), 3.56 (s,3H), 3.72 (s, 3H), 3.86 (s, 1H), 6.76 (d, J = 2.3 Hz, 1H), 6.82 (d, J =8.2 Hz, 1H), 6.87 (d, J = 8.2 Hz, 1H), 6.89 (dd, J = 8.1, 2.3 Hz, 1H),7.25 (d, J = 8.1 Hz, 1H), 7.52-7.56 (m, 2H), 7.66 (tt, J = 7.4, 1.4 Hz,1H), 8.23 (dd, J = 8.2, 1.4 Hz, 2H), 9.60 (s, 1H)

Reference Example 38-Hydroxymethyl-7-(2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 3-1)

Lithium aluminium hydride (26.0 mg, 0.64 mmol) was suspended inanhydrous tetrahydrofuran (0.5 mL) under nitrogen atmosphere. Ananhydrous tetrahydrofuran solution (1.5 mL) of8-methoxycarbonyl-7-(2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 2-1, 108 mg, 0.32 mmol) was added thereto at 0°C., and stirred for 3 hours at the same temperature. After ethyl acetate(3 mL) and water (3 mL) were added dropwise successively, ethyl acetate(30 mL), water (30 mL) and 1N aqueous hydro chloride solution (5 mL)were added thereto, and the mixture was partitioned. After the waterlayer was extracted with ethyl acetate (20 mL), the organic layer wascombined. The organic layer was washed with water (50 mL, 2 times) andsaturated brine (50 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled reference compound (61.0 mg)as a pale yellow amorphous product. (Yield 61%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.39 (s, 3H), 1.50 (s, 3H), 3.77 (s, 3H),4.44 (d, J = 6.3 Hz, 2H), 6.69 (d, J = 8.0 Hz, 1H), 6.75 (d, J = 8.0 Hz,1H), 6.97 (d, J = 8.2 Hz, 1H), 7.04 (td, J = 7.4, 1.1 Hz, 1H), 7.18 (dd,J = 7.4, 1.8 Hz, 1H), 7.34 (ddd, J = 8.2, 7.4, 1.8 Hz, 1H), 8.57 (br s,1H)Using any compounds among Reference Compounds No. 2-2˜2-5, the followingReference Compounds (No. 3-2˜3-5) were obtained by a method similar tothat of Reference Compound No. 3-1.

7-(4-Fluoro-2-methoxyphenyl)-8-hydroxymethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 3-2)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.24 (s, 3H), 1.27 (s, 3H), 3.70 (s, 3H),4.18 (dd, J = 12.9, 5.0 Hz, 1H), 4.44 (dd, J = 12.9, 5.0 Hz, 1H), 5.29(t, J = 5.0 Hz, 1H), 6.07 (s, 1H), 6.57 (d, J = 8.1 Hz, 1H), 6.66 (d, J= 8.1 Hz, 1H), 6.79 (td, J = 8.4, 2.5 Hz, 1H), 6.94 (dd, J = 11.5, 2.5Hz, 1H), 7.12 (dd, J = 8.4, 7.1 Hz, 1H), 9.24 (s, 1H)7-(5-Fluoro-2-methoxyphenyl)-8-hydroxymethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 3-3)  

1H-NMR (400 MHz, DMSO-d₆) δ 1.25 (s, 3H), 1.28 (s, 3H), 3.67 (s, 3H),4.20 (dd, J = 12.8, 5.3 Hz, 1H), 4.46 (dd, J = 12.8, 5.3 Hz, 1H), 5.30(t, J = 5.3 Hz, 1H), 6.11 (s, 1H), 6.61 (d, J = 8.1 Hz, 1H), 6.67 (d, J= 8.1 Hz, 1H), 6.97 (dd, J = 9.0, 3.2 Hz, 1H), 7.03 (dd, J = 8.9, 4.8Hz, 1H), 7.14 (td, J = 8.9, 3.2 Hz, 1H), 9.25 (s, 1H)8-Hydroxymethyl-7-(2-methoxy-4-methoxymethoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No.3-4)  

¹H-NMR (400 MHz, CDCl₃) δ 1.38 (s, 3H), 1.49 (s, 3H), 2.13 (t, J = 6.9Hz, 1H), 3.53 (s, 3H), 3.75 (s, 4H), 4.45 (d, J = 6.9 Hz, 2H), 5.22 (s,2H), 6.67 (d, J = 2.7 Hz, 1H), 6.67 (d, J = 8.1 Hz, 1H), 6.72 (dd, J =8.0, 2.7 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H),8.57 (s, 1H) 7-(4-Hydroxy-2-methoxyphenyl)-8-hydroxymethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 3-5)  

¹H-NMR (400 MHz, CDCl₃) δ 1.39 (s, 3H), 1.49 (s, 3H), 2.07 (t, J = 6.5Hz, 1H), 3.74 (s, 4H), 4.45 (d, J = 6.5 Hz, 2H), 4.95 (s, 1H), 6.48 (dd,J = 7.8, 2.3 Hz, 1H), 6.50 (d, J = 2.3 Hz, 1H), 6.67 (d, J = 8.1 Hz,1H), 6.72 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 7.8 Hz, 1H), 8.56 (s, 1H)

Reference Example 48-Chloromethyl-7-(4-fluoro-2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 4-1)

7-(4-Fluoro-2-methoxyphenyl)-8-hydroxymethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 3-2, 70.0 mg, 0.21 mmol) was dissolved in themixed solvent of anhydrous dichloromethane (1 mL) and anhydroustetrahydrofuran (1.5 mL), and triethylamine (35 μL, 0.25 mmol) andmethanesulfonyl chloride (18 μL, 0.23 mmol) were added theretosuccessively. The reaction mixture was stirred at room temperatureovernight. Ethyl acetate (30 mL) and water (30 mL) were added to thereaction mixture and partitioned. The organic layer was washed withwater (30 mL) and saturated brine (30 mL) successively, dried overanhydrous magnesium sulfate, and then the solvent was removed underreduced pressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled referencecompound (49.5 mg) as pale yellow solid. (Yield 68%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.19 (s, 3H), 1.30 (s, 3H), 3.70 (s, 3H),4.29 (d, J = 11.7 Hz, 1H), 4.91 (d, J = 11.7 Hz, 1H), 6.18 (s, 1H), 6.59(d, J = 8.1 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.82 (td, J = 8.4, 2.4Hz, 1H), 6.97 (dd, J = 11.5, 2.4 Hz, 1H), 7.14 (dd, J = 8.4, 7.1 Hz,1H), 9.77 (s, 1H)Using any compounds among Reference Compounds No. 3-3 and 3-4, thefollowing Reference Compounds (No. 4-2 and 4-3) were obtained by amethod similar to that of Reference Compound No. 4-1.

8-Chloromethyl-7-(5-fluoro-2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 4-2)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.19 (s, 3H), 1.30 (s, 3H), 3.67 (s, 3H),4.31 (d, J = 11.7 Hz, 1H), 4.95 (d, J = 11.7 Hz, 1H), 6.22 (s, 1H), 6.63(d, J = 8.1 Hz, 1H), 6.75 (d, J = 8.1 Hz, 1H), 6.99 (dd, J = 9.0, 3.2Hz, 1H), 7.07 (dd, J = 8.9, 4.6 Hz, 1H), 7.19 (td, J = 8.9, 3.2 Hz, 1H),9.80 (s, 1H) 8-Chloromethyl-7-(2-methoxy-4-methoxymethoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No.4-3)  

¹H-NMR (400 MHz, CDCl₃) δ 1.44 (s, 3H), 1.45 (s, 3H), 3.53 (s, 3H), 3.74(s, 4H), 4.42 (s, 2H), 5.22 (s, 2H), 6.66 (d, J = 2.3 Hz, 1H), 6.70 (d,J = 8.1 Hz, 1H), 6.70 (dd, J = 8.3, 2.3 Hz, 1H), 6.77 (d, J = 8.1 Hz,1H), 7.11 (d, J = 8.3 Hz, 1H), 7.85 (br s, 1H)

Reference Example 57-Bromo-8-hydroxymethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 5)

Lithium aluminium hydride (38.5 mg, 1.01 mmol) was suspended inanhydrous tetrahydrofuran (0.5 mL) under nitrogen atmosphere. Ananhydrous tetrahydrofuran solution (1.5 mL) of7-bromo-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 1, 101 mg, 0.323 mmol) was added dropwisethereto at 0° C., and stirred for 1 hour at the same temperature. Ethylacetate (10 mL), water (10 mL), and 1N aqueous hydrochloride solution (2mL) were added thereto successively and the mixture was partitioned. Theorganic layer was washed with saturated brine (10 mL), dried overanhydrous magnesium sulfate, and then the solvent was removed underreduced pressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled referencecompound (67.4 mg) as an orange amorphous product. (Yield 74%)

¹H-NMR (400 MHz, CDCl₃) δ 1.39 (s, 6H), 3.18 (br s, 1H), 3.75 (s, 1H),4.99 (d, J = 9.5 Hz, 2H), 6.51 (d, J = 8.3 Hz, 1H), 7.07 (d, J = 8.3 Hz,1H), 9.40 (s, 1H)

Reference Example 67-Bromo-8-hydroxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 6)

A mixture of7-bromo-8-hydroxymethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 5, 62.7 mg, 0.220 mmol), methyl iodide (68.6 μL,1.10 mmol), and cessium carbonate (180 mg, 0.552 mmol) was suspended inanhydrous N,N-dimethylformamide (1 mL) and stirred at room temperaturefor 2.5 hours. Ethyl acetate (10 mL) and water (10 mL) were added to thereaction mixture and partitioned. The organic layer was washed withsaturated brine (10 mL), dried over anhydrous magnesium sulfate, andthen the solvent was removed under reduced pressure. The obtainedresidue was purified by silica gel column chromatography (hexane-ethylacetate) to give the titled reference compound (45.5 mg) as an orangeamorphous product. (Yield 69%)

¹H-NMR (400 MHz, CDCl₃) δ 1.31 (s, 6H), 3.56 (s, 3H), 3.77 (br s, 1H),4.73 (d, J = 7.1 Hz, 2H), 6.57 (d, J = 8.4 Hz, 1H), 7.17 (d, J = 8.4 Hz,1H)

Reference Example 77-Bromo-8-chloromethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 7)

7-Bromo-8-hydroxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 6, 37.5 mg, 0.125 mmol 1) was dissolved inanhydrous dichloromethane (1 mL), and triethylamine (20.9 μL, 0.150mmol) and methanesulfonyl chloride (10.7 μL, 0.138 mmol) were addedthereto successively. The reaction mixture was stirred at roomtemperature overnight. Ethyl acetate (10 mL) and water (10 mL) wereadded to the reaction mixture and partitioned. The organic layer waswashed with saturated brine (10 mL), dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled reference compound (28.7 mg)as an orange amorphous product. (Yield 72%)

¹H-NMR (400 MHz, CDCl₃) δ 1.30 (s, 6H), 3.55 (s, 3H), 3.76 (br s, 1H),4.76 (s, 2H), 6.61 (d, J = 8.4 Hz, 1H), 7.23 (d, J = 8.4 Hz, 1H)

Reference Example 87-Bromo-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 8-1)

A mixture of7-bromo-8-chloromethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 7, 801 mg, 2.52 mmol), 5-fluoro-2-methylphenol(330 μL, 3.02 mmol), and potassium carbonate (524 mg, 3.79 mmol) wassuspended in anhydrous N,N-dimethylformamide (10 mL) and stirred at 80°C. overnight. After cooling down, ethyl acetate (80 mL) and water (50mL) were added to the reaction mixture and partitioned. The organiclayer was washed with saturated brine (50 mL), dried over anhydrousmagnesium sulfate, and then the solvent was removed under reducedpressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled referencecompound (945 mg) as a colorless solid. (Yield 92%)

¹H-NMR (400 MHz, CDCl₃) δ 1.24 (s, 6H), 2.13 (s, 3H), 3.41 (s, 3H), 3.78(br s, 1H), 5.16 (s, 2H), 6.54-6.57 (m, 1H), 6.58 (d, J = 9.5 Hz, 1H) ,6.62 (d, J = 8.5 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 7.23 (d, J = 8.5 Hz,1H)Using any compounds among Reference Compounds No. 7 and availablecompounds, the following Reference Compounds (No. 8-2˜8-4) were obtainedby a method similar to that of Reference Compound No. 8-1.

¹H-NMR (400 MHz, CDCl₃) δ 1.23 (s, 6H), 2.20 (s, 3H), 3.43 (s, 3H), 3.76(br s, 1H), 5.18 (s, 2H), 6.61 (d, J = 8.4 Hz, 1H), 6.83 (d, J = 8.1 Hz,1H), 6.86 (t, J = 7.2 Hz, 1H), 7.12-7.16 (m, 1H), 7.23 (d, J = 8.4 Hz,1H), 7.26-7.27 (m, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.29 (s, 6H), 3.50 (s, 3H), 3.74 (s, 1H), 3.84(s, 3H), 4.30 (d, J = 5.6 Hz, 2H), 4.73 (t, J = 5.6 Hz, 1H), 6.57 (d, J= 8.3 Hz, 1H), 6.67 (dd, J = 7.8, 1.5 Hz, 1H), 6.72 (td, J = 7.8, 1.5Hz, 1H), 6.80 (dd, J = 7.8, 1.5 Hz, 1H), 6.89 (td, J = 7.8, 1.5 Hz, 1H),7.21 (d, J = 8.3 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.30 (s, 6H), 2.11 (s, 3H), 3.47 (s, 3H), 3.78(s, 1H), 4.12 (br s, 1H), 4.30 (d, J = 5.5 Hz, 2H), 6.35- 6.40 (m, 2H) ,6.60 (d, J = 8.6 Hz, 1H), 6.98 (t, J = 7.2 Hz, 1H), 7.22 (d, J = 8.6 Hz,1H)

Reference Example No. 97-Bromo-8-methoxycarbonyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 9)

A mixture of7-bromo-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 1, 102 mg, 0.326 mmol), methyl iodide (100 μL,1.60 mmol), and cessium carbonate (272 mg, 0.835 mmol) was suspended inanhydrous N,N-dimethylformamide (5 mL) and stirred at room temperaturefor 2 hours. Ethyl acetate (25 mL) and water (25 mL) were added to thereaction mixture and partitioned. The organic layer was washed withsaturated brine (20 mL), dried over anhydrous magnesium sulfate, andthen the solvent was removed under reduced pressure. The obtainedresidue was purified by silica gel column chromatography (hexane-ethylacetate) to give the titled reference compound (86.0 mg) as a paleyellow solid. (Yield 83%)

¹H-NMR (500 MHz, CDCl₃) δ 1.34 (s, 6H), 3.27 (s, 3H), 3.85 (br s, 1H),3.95 (s, 3H), 6.64 (d, J = 8.2 Hz, 1H), 7.15 (d, J = 8.2 Hz, 1H)

Reference Example 107-(5-Chloro-2-methoxyphenyl)-8-methoxycarbonyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 10-1)

A mixture of7-bromo-8-methoxycarbonyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 9, 3.75 g, 11.5 mmol),5-chloro-2-methoxyphenylboronic acid (2.57 g, 13.8 mmol), cessiumcarbonate (7.49 g, 23.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.33 g, 1.16 mmol) was suspended in anhydrous N,N-dimethylformamide(70 ml) and stirred at 80° C. overnight under argon atmosphere. Aftercooling down, ethyl acetate (300 mL), diethylether (150 mL) and water(400 mL) were added and partitioned. The organic layer was washed withwater (250 mL) and saturated brine (150 mL) successively, dried overanhydrous magnesium sulfate, and then the solvent was removed underreduced pressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled referencecompound (3.84 g) as a colorless amorphous product. (Yield 86%)

¹H-NMR (400 MHz, CDCl₃) δ 1.39 (s, 3H), 1.41 (s, 3H), 3.21 (s, 3H), 3.61(s, 3H), 3.72 (s, 3H), 3.91 (s, 1H), 6.80 (d, J = 8.1 Hz, 1H), 6.82 (d,J = 8.6 Hz, 1H), 6.87 (d, J = 8.1 Hz, 1H), 7.14 (d, J = 2.5 Hz, 1H),7.25 (dd, J = 8.6, 2.5 Hz, 1H)Using any compounds among Reference Compounds No. 9 and availablecompounds, the following Reference Compound (No. 10-2) was obtained by amethod similar to that of Reference Compound No. 10-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 1.21 (s, 3H), 1.25 (s, 3H), 3.02 (s, 3H),3.54 (s, 3H), 3.67 (s, 3H), 6.45 (s, 1H), 6.76 (td, J = 8.3, 2.5 Hz,1H), 6.79 (d, J = 8.3 Hz, 1H), 6.90 (dd, J = 11.4, 2.5 Hz, 1H), 6.91 (d,J = 8.3 Hz, 1H), 7.04 (dd, J = 8.3, 7.1 Hz, 1H)

Reference Example 119-Chloro-2,2,4-trimethyl-1,4-dihydro-2H-6-oxa-1,4-diazachrysen-3,5-dione(Reference Compound No. 11-1)

7-(5-Chloro-2-methoxyphenyl)-8-methoxycarbonyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 10-1, 3.81 g, 9.80 mmol) was dissolved inanhydrous dichloromethane (30 mL), boron tribromide (7.62 g, 30.4 mmol)was added thereto at −78° C., and then stirred at room temperature for 1hour. The reaction mixture was poured into ice water (500 mL), ethylacetate (500 mL) was added thereto and partitioned. The organic layerwas washed with saturated brine (200 mL), dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was dissolved in N,N-dimethylformamide (50 mL), 60%sodium hydride (23.1 mg, 0.578 mmol) was added thereto, and then stirredat 70° C. overnight. 60% sodium hydride (31.2 mg, 0.780 mmol) was addedmore thereto and stirred at 80° C. overnight. After cooling down, ethylacetate (200 mL), diethylether (200 mL) and water (300 mL) were addedand partitioned. The organic layer was washed with water (200 mL) andsaturated brine (200 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was filtered with ethyl acetate/hexane (1/4, 30 mL) togive the titled reference compound (2.04 g) as a pale yellow solid.(Yield 61%)

¹H-NMR (400 MHz, CDCl₃) δ 1.40 (s, 6H), 3.33 (s, 3H), 4.25 (br s, 1H),7.17 (d, J = 8.5 Hz, 1H), 7.25 (d, J = 8.4 Hz, 1H), 7.34 (dd, J = 8.4,2.4 Hz, 1H), 7.68 (d, J = 8.5 Hz, 1H), 7.89 (d, J = 2.4 Hz, 1H)Using Reference Compound No. 10-2, the following Reference Compound (No.11-2) was obtained by a method similar to that of Reference Compound No.11-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 1.23 (s, 6H), 3.15 (s, 3H), 6.97 (s, 1H),7.23 (td, J = 8.9, 2.6 Hz, 1H), 7.32 (dd, J = 8.3, 2.6 Hz, 1H), 7.34 (d,J = 8.5 Hz, 1H), 7.97 (d, J = 8.5 Hz, 1H), 8.23 (dd, J = 8.9, 6.1 Hz,1H)

Reference Example 127-(5-Chloro-2-hydroxyphenyl)-8-hydroxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 12-1)

Lithium aluminium hydride (442 mg, 11.7 mmol) was suspended in anhydroustetrahydrofuran (10 mL) under nitrogen atmosphere. An anhydroustetrahydrofuran solution (40 mL) of9-chloro-2,2,4-trimethyl-1,4-dihydro-2H-6-oxa-1,4-diazachrysen-3,5-dione(Reference Compound No. 11-1, 1:99 g, 5.81 mmol) was added dropwisethereto at −10° C. and stirred for 10 minutes at the same temperature.After ethyl acetate (1 mL) and water (1 mL) were added theretosuccessively, ethyl acetate (300 mL) and saturated brine (300 mL) wereadded and partitioned. The organic layer was washed with saturated brine(150 mL), dried over anhydrous magnesium sulfate, and then the solventwas removed under reduced pressure. The obtained residue was purified bysilica gel column chromatography (hexane-ethyl acetate) to give thetitled reference compound (1.38 g) as a pale yellow solid. (Yield 69%)

¹H-NMR (400 MHz, CDCl₃) δ 1.24 (s, 3H), 1.45 (s, 3H), 2.25 (br s, 1H),3.62 (s, 3H), 3.85 (s, 1H), 4.46 (d, J = 11.5 Hz, 1H), 4.57 (dd, J =11.5, 3.8 Hz, 1H), 5.92 (br s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 6.84 (d, J= 7.8 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 7.14 (d, J = 2.4 Hz, 1H), 7.26(dd, J = 8.4, 2.4 Hz, 1H)Using Reference Compound No. 11-2, the following Reference Compound (No.12-2) was obtained by a method similar to that of Reference Compound No.12-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 1.17 (s, 6H), 3.32 (s, 3H), 4.12- 4.69 (m,3H), 6.02 (s, 1H), 6.60-6.70 (m, 2H), 6.68 (d, J = 8.1 Hz, 1H), 6.74 (d,J = 8.1 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 9.76 (s, 1H)

Reference Example 137-(5-Chloro-2-methoxyphenyl)-8-hydroxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 13-1)

A mixture of7-(5-chloro-2-hydroxyphenyl)-hydroxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 12-1, 1.36 g, 3.92 mmol), methyl iodide (244 μL,3.92 mmol), and potassium carbonate (1.08 g, 7.81 mmol) was suspended inanhydrous N,N-dimethylformamide (20 mL) and stirred at 50° C. for 1hour. After cooling down, ethyl acetate (70 mL), diethylether (70 mL),and water (150 mL) were added and partitioned. The organic layer waswashed with water (100 mL) and saturated brine (50 mL) successively,dried over anhydrous magnesium sulfate, and then the solvent was removedunder reduced pressure. The obtained residue was purified by silica gelcolumn chromatography (hexane-ethyl acetate) to give the titledreference compound (1.36 g) as a pale yellow amorphous product. (Yield96%)

¹H-NMR (400 MHz, CDCl₃) δ 1.21 (s, 3H) , 1.47 (s, 3H), 2.79 (dd, J =9.0, 3.3 Hz, 1H), 3.65 (s, 3H), 3.77 (s, 1H), 3.78 (s, 3H), 4.35 (dd, J= 12.5, 3.3 Hz, 1H), 4.45 (dd, J = 12.5, 9.0 Hz, 1H), 6.73 (d, J = 7.9Hz, 1H), 6.78 (d, J = 7.9 Hz, 1H), 6.95 (d, J = 8.8 Hz, 1H), 7.17 (d, J= 2.6 Hz, 1H), 7.34 (dd, J = 8.8, 2.6 Hz, 1H)Using Reference Compound No. 12-2, the following Reference Compound (No.13-2) was obtained by a method similar to that of Reference Compound No.13-1.

¹H-NMR (500 MHz, DMSO-d₆) δ 1.12 (s, 3H), 1.23 (s, 3H), 3.36 (s, 3H),3.72 (s, 3H), 4.17 (d, J = 11.9 Hz, 1H), 4.47 (dd, J = 11.9, 5.0 Hz,1H), 4.60 (t, J = 5.0 Hz, 1H), 6.04 (s, 1H), 6.67 (d, J = 7.9 Hz, 1H),6.73 (d, J = 7.9 Hz, 1H), 6.80 (td, J = 8.4, 2.4 Hz, 1H), 6.94 (dd, J =11.6, 2.4 Hz, 1H), 7.20 (dd, J = 8.4, 7.0 Hz, 1H)

Reference Example 147-(5-Chloro-2-methoxyphenyl)-8-chloromethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 14-1)

7-(5-Chloro-2-methoxyphenyl)-8-hydroxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 13-1, 1.34 g, 3.71 mmol) was dissolved inanhydrous dichloromethane (19 mL), and triethylamine (621 μL, 4.46 mmol)and methanesulfonyl chloride (316 μL, 4.08 mmol) were added theretosuccessively. The reaction mixture was stirred at room temperatureovernight. Ethyl acetate (200 mL) was added to the reaction mixture,washed with water (200 mL), dried over anhydrous magnesium sulfate, andthen the solvent was removed under reduced pressure. The obtainedresidue was purified by silica gel column chromatography (hexane-ethylacetate) to give the titled reference compound (1.14 g) as a colorlessamorphous product. (Yield 81%)

¹H-NMR (500 MHz, CDCl₃) δ 1.27 (s, 3H), 1.41 (s, 3H), 3.52 (s, 3H), 3.74(s, 3H), 3.80 (s, 1H), 4.45 (d, J = 12.5 Hz, 1H), 4.66 (d, J = 12.5 Hz,1H), 6.75 (d, J = 8.1 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H), 6.88 (d, J =8.9 Hz, 1H), 7.24 (d, J = 2.7 Hz, 1H), 7.32 (dd, J = 8.9, 2.7 Hz, 1H)Using Reference Compound No. 13-2, the following Reference Compound (No.14-2) was obtained by a method similar to that of Reference Compound No.14-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 1.11 (s, 3H), 1.24 (s, 3H), 3.36 (s, 3H),3.74 (s, 3H), 4.44 (d, J = 12.8 Hz, 1H), 4.77 (d, J = 12.8 Hz, 1H), 6.24(s, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 6.85 (td, J= 8.4, 2.5 Hz, 1H), 6.99 (dd, J = 11.3, 2.5 Hz, 1H), 7.21 (dd, J = 8.4,7.1 Hz, 1H)

Reference Example 15 4-Benzoyloxyanisole (Reference Compound No. 15-1)

4-Hydroxyanisole (1.25 g, 10.1 mmol) was dissolved in anhydrousdichloromethane (10 mL), and triethylamine (4.25 mL, 30.5 mmol) andbenzoyl chloride (1.40 mL, 12.1 mmol) were added thereto successively.The reaction mixture was stirred at room temperature for 4 hours.Chloroform (50 mL) and water (50 mL) were added to the reaction mixtureand partitioned. The organic layer was washed with saturated brine (50mL), dried over anhydrous magnesium sulfate, and then the solvent wasremoved under reduced pressure. The obtained residue was filtered withhexane (50 mL) to give the titled reference compound (2.24 g) as acolorless solid. (Yield 98%)

¹H-NMR (400 MHz, DMSO-d₆) δ 3.78 (s, 3H), 7.01 (d, J = 9.1 Hz, 2H), 7.21(d, J = 9.1 Hz, 2H), 7.61 (t, J = 7.8 Hz, 2H), 7.75 (t, J = 7.8 Hz, 1H),8.13 (d, J = 7.8 Hz, 2H)Using Reference Compound No. 16-3, the following Reference Compound (No.15-2) was obtained by a method similar to that of Reference Compound No.15-1.

¹H-NMR (400 MHz, CDCl₃) δ 3.89 (s, 3H), 6.65 (dd, J = 8.5, 2.4 Hz, 1H),6.73 (d, J = 2.4 Hz, 1H), 7.50-7.54 (m, 2H), 7.63-7.68 (m, 1H), 7.80 (d,J = 8.5 Hz, 1H), 8.18-8.21 (m, 2H)

Reference Example 16 2-Bromo-4-chloro-5-fluoroaisole (Reference CompoundNo. 16-1)

A mixture of 4-chloro-3-fluoroanisole (124 μL, 1.00 mmol) andN-bromosuccinimide was dissolved in mixed solvent of anhydrousN,N-dimethylformamide (0.5 mL) and anhydrous dichloromethane (1 mL), andstirred at 40° C. for 3 days. After cooling down, chloroform (30 mL) andwater (30 mL) were added and partitioned. The water layer was extractedwith chloroform (30 mL, 2 times). The combined organic layer was washedwith saturated brine (30 mL), dried over anhydrous magnesium sulfate,and then the solvent was removed under reduced pressure. The obtainedresidue was purified by silica gel column chromatography (hexane-ethylacetate) to give the titled reference compound (195 mg) as a colorlesssolid. (Yield 82%)

¹H-NMR (500 MHz, DMSO-d₆) δ 3.88 (s, 3H), 7.32 (d, J = 11.3 Hz, 1H),7.87 (d, J = 8.2 Hz, 1H)Using any compounds among Reference Compounds No. 15-1 and availablecompounds, the following Reference Compounds (No. 16-2˜16-3) wereobtained by a method similar to that of Reference Compound No. 16-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 3.88 (s, 3H), 7.19 (d, J = 9.0 Hz, 1H), 7.32(dd, J = 9.0, 2.8 Hz, 1H), 7.59-7.63 (m, 3H), 7.75 (tt, J = 7.8, 1.5 Hz,1H), 8.12 (dt, J = 7.8, 1.5 Hz, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 3.85 (s, 3H), 4.82 (s, 1H), 6.25 (dd, J = 8.4,2.7 Hz, 1H), 6.40 (d, J = 2.7 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H)

Reference Example 17 5-Chloro-4-fluoro-2-methoxyphenylboronic acid(Reference Compound No. 17)

2-Bromo-4-chloro-5-fluoroanisole (Reference Compound No. 16-1, 239 mg,1.00 mmol) was dissolved in mixed solvent of anhydrous toluene (2 mL)and anhydrous tetrahydrofuran (0.5 mL), 1.6M hexane solution of n-butyllithium (750 μL, 1.20 mmol) was added thereto at −40° C., and then thereaction mixture was stirred at the same temperature for 30 minutes.Triisopropyl boronic acid (277 μL, 1.20 mmol) was added dropwise to thereaction mixture, warmed to −20° C. over 10 minutes, and then 2N aqueousHCl solution (1 mL) was added. After the reaction mixture was stirred atroom temperature for 20 minutes, ethyl acetate (20 mL) and water (20 mL)were added and partitioned. The organic layer was washed with saturatedbrine (20 mL), dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure to give the titled referencecompound (181 mg) as a colorless solid. (Yield 89%)

¹H-NMR (400 MHz, DMSO-d₆) δ 3.81 (s, 3H), 7.10 (d, J = 12.2 Hz, 1H),7.57 (d, J = 9.5 Hz, 1H), 7.86 (br s, 1H), 8.45 (br s, 1H)

Reference Example 182-(5,5-Dimethyl[1,3,2]dioxaborinan-2-yl)-4-nitroanisole (ReferenceCompound No. 18-1)

A mixture of 2-Bromo-4-nitroanisole (100 mg, 0.431 mmol),bis(neopentylglycolate)diborane (151 mg, 0.668 mmol), potassium acetate(129 mg, 1.31 mmol), and[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloridedichloromethane complex (1:1) (35.5 mg, 0.0435 mmol) was suspended indimethylsulfoxide (3 mL), and the reaction mixture was stirred at 80° C.for 10 minutes under microwave. After cooling down, ethyl acetate (30mL) and water (30 mL) were added to the reaction mixture andpartitioned. The organic layer was washed with saturated brine (30 mL),dried over anhydrous magnesium sulfate, and then the solvent was removedunder reduced pressure to give the titled reference compound (72.5 mg)as a yellow solid. (Yield 85%)

¹H-NMR (500 MHz, DMSO-d₆) δ 3.89 (s, 3H), 7.35 (d, J = 9.4 Hz, 1H), 8.12(d, J = 2.7 Hz, 1H), 8.34 (dd, J = 9.4, 2.7 Hz, 1H)Using any compounds among Reference Compounds No. 15-2, 16-2, 23 andavailable compounds, the following Reference Compounds (No. 18-2˜18-7)were obtained by method similar to that of Reference Compound No. 18-1.

¹H-NMR (500 MHz, DMSO-d₆) δ 0.98 (s, 6H), 3.47 (s, 4H), 3.86 (s, 3H),7.67 (d, J = 1.9 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.77 (dd, J = 8.0,1.9 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 3.93 (s, 3H), 5.63 (s, 2H), 6.83 (d, J = 2.1Hz, 1H), 6.91 (dd, J = 8.0, 2.1 Hz, 1H), 7.53 (t, J = 7.9 Hz, 2H),7.64-7.67 (m, 1H), 7.91 (d, J = 8.0 Hz, 1H), 8.20-8.22 (m, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 3.94 (s, 3H), 5.92 (s, 2H), 6.96 (d, J = 8.9Hz, 1H), 7.30 (dd, J = 8.9, 3.0 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.63(tt, J = 7.8, 1.5 Hz, 1H), 7.66 (d, J = 3.0 Hz, 1H), 8.20 (dd, J = 7.8,1.5 Hz, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 3.49 (s, 3H), 3.90 (s, 3H), 5.21 (s, 2H), 5.58(s, 2H), 6.60 (d, J = 2.0 Hz, 1H), 6.70 (dd, J = 8.2, 2.0 Hz, 1H), 7.75(d, J = 8.2 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 4.03 (s, 3H), 5.68 (s, 2H), 7.75 (d, J = 1.8Hz, 1H), 7.89 (dd, J = 8.1, 1.8 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.06 (s, 6H), 3.81 (s, 4H), 3.94 (s, 3H), 6.91(d, J = 9.2 Hz, 1H), 8.26 (dd, J = 9.2, 3.0 Hz, 1H), 8.55 (d, J = 3.0Hz, 1H)

Reference Example 19 5-Cyano-2-trifluoromethylsulfonyloxyanisole(Reference Compound No. 19-1)

A mixture of 5-cyano-2-hydroxyanisole (600 mg, 4.02 mmol) andtriethylamine (1.40 mL, 10.0 mmol) was dissolved in anhydroustetrahydrofuran (20 mL) under argon atmosphere. Trifluoromethanesulfonylchloride (642 μL, 6.03 mmol) were added thereto at −10° C., and stirredat the same temperature for 1 hour. Ethyl acetate (100 mL) and water(100 mL) were added to the reaction mixture and partitioned. The organiclayer was washed with saturated brine (50 mL), dried over anhydrousmagnesium sulfate, and then the solvent was removed under reducedpressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled referencecompound (979 mg) as a colorless solid. (Yield 87%)

¹H-NMR (400 MHz, DMSO-d₆) δ 3.97 (s, 3H), 7.61 (dd, J = 8.4, 1.9 Hz,1H), 7.72 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 1.9 Hz, 1H)Using available compounds, the following Reference Compounds (No.19-2˜19-4) were obtained by a method similar to that of ReferenceCompound No. 19-1.

¹H-NMR (400 MHz, CDCl₃) δ 2.62 (s, 3H), 3.99 (s, 3H), 7.32 (d, J = 8.5Hz, 1H), 7.57 (dd, J = 8.5, 2.0 Hz, 1H), 7.66 (d, J = 2.0 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 2.37 (s, 3H), 3.89 (s, 3H), 6.75- 6.77 (m,1H), 6.83 (d, J = 1.7 Hz, 1H), 7.08 (d, J = 8.3 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 3.91 (s, 3H), 3.98 (s, 3H), 7.07 (d, J = 8.6Hz, 1H), 7.89 (d, J = 2.1 Hz, 1H), 8.05 (dd, J = 8.6, 2.1 Hz, 1H)

Reference Example 205-Cyano-2-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)anisole(Reference Compound No. 20-1)

A mixture of 5-cyano-2-trifluoromethylsulfonyloxyanisole (ReferenceCompound No. 19-1, 200 mg, 0.711 mmol), bis(pinacolato)diboron (200 mg,0.788 mmol), potassium acetate (213 mg, 2.17 mmol), and[1,1′-bis(diphenylphosphino)ferrocene] (20.0 mg, 0.0361 mmol), and[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloridedichloromethane complex (1:1) (29.4 mg, 0.0360 mmol) was suspended in1,4-dioxane (4 mL), and the reaction mixture was stirred at 80° C.overnight. After cooling down, ethyl acetate (100 mL) and water (100 mL)were added and partitioned. The organic layer was washed with saturatedbrine (50 mL), dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. The obtained residue waspurified by silica gel column chromatography (hexane-ethyl, acetate) togive the titled reference compound (123 mg) as a colorless solid. (Yield67%)

¹H-NMR (500 MHz, CDCl₃) δ 1.36 (s, 12H), 3.86 (s, 3H), 7.06 (s, 1H),7.23 (d, J = 7.5 Hz, 1H), 7.72 (d, J = 7.5 Hz, 1H)Using Reference Compound No. 19-4, the following Reference Compound (No.20-2) was obtained by a method similar to that of Reference Compound No.20-1.

¹H-NMR (500 MHz, CDCl₃) δ 1.36 (s, 12H), 3.88 (s, 3H), 3.89 (s, 3H),6.88 (d, J = 8.8 Hz, 1H), 8.10 (dd, J = 8.8, 2.4 Hz, 1H), 8.34 (d, J =2.4 Hz, 1H)

Reference Example 217-(5,5-Dimethyl[1,3,2]dioxaborinan-2-yl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound 21)

A mixture of7-bromo-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 8-1, 98.7 mg, 0.242 mmol), bis(neopentylglycolate)diboron (170 mg, 0.753 mmol), potassium acetate (112 mg, 1.14mmol), and [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloridedichloromethane complex (1:1) (20.7 mg, 0.0253 mmol) was suspended indimethylsulfoxide (2 mL), and the reaction mixture was stirred at 80° C.for 15 minutes under microwave. After cooling down, ethyl acetate (15mL) and water (15 mL) were added to the reaction mixture andpartitioned. The organic layer was washed with saturated brine (15 mL),dried over anhydrous magnesium sulfate, and then the solvent was removedunder reduced pressure. The obtained residue was purified by silica gelcolumn chromatography (1st: hexane-ethyl acetate, 2nd:chloroform). Theobtained residue was filtered with hexane (5 ml) to give the titledreference compound (70.2 mg) as a colorless solid. (Yield 65%)

¹H-NMR (400 MHz, CDCl₃) δ 0.95 (s, 6H), 1.25 (s, 6H), 2.08 (s, 3H), 3.38(s, 3H), 3.64 (s, 4H), 3.86 (s, 1H), 5.36 (s, 2H), 6.52 (td, J = 8.3,2.4 Hz, 1H), 6.59 (dd, J = 11.2, 2.4 Hz, 1H), 6.69 (d, J = 7.8 Hz, 1H),7.01 (t, J = 7.6 Hz, 1H), 7.47 (d, J = 7.8 Hz, 1H)

Reference Example 228-(5-Fluoro-2-methylphenoxymethyl)-7-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 22)

A mixture of7-bromo-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 8-1, 101 mg, 0.248 mmol), bis(pinacolato)diboron(156 mg, 0.614 mmol), potassium acetate (75.5 mg, 0.769 mmol),1,1′-bis(diphenylphosphino)ferrocene (7.2 mg, 0.013 mmol), and[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloridedichloromethane complex (1:1) (10.7 mg, 0.0131 mmol) was suspended in1,4-dioxane (2 mL), and the reaction mixture was stirred at 80° C.overnight. After cooling down, ethyl acetate (15 mL) and water (15 mL)were added and partitioned. The organic layer was washed with saturatedbrine (15 mL), dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. The obtained residue waspurified by silica gel column chromatography (1st:hexane-ethyl acetate,2nd:chloroform-methanol) to give the titled reference compound (87.9 mg)as a colorless amorphous product. (Yield 78%)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 12H), 1.25 (s, 6H), 2.07 (s, 3H),3.41 (s, 3H), 3.92 (s, 1H), 5.37 (s, 2H), 6.50-6.57 (m, 1H), 6.64 (dd, J= 11.0, 2.4 Hz, 1H), 6.70 (d, J = 7.6 Hz, 1H), 6.94-7.05 (m, 1H), 7.53(d, J = 7.9 Hz, 1H)

Reference Example 23 2-Bromo-5-methoxymethoxyanisole (Reference CompoundNo. 23)

A mixture of 4-bromo-3-methoxyphenol (500 mg, 2.46 mmol),chlorodimethylether (281 μL, 3.70 mmol), and potassium carbonate (850mg, 6.15 mmol) was suspended in anhydrous N,N-dimethylformamide (8 mL)and stirred at 50° C. for 1 hour. After cooling down, the reactionmixture was diluted with ethyl acetate (150 mL). The mixture was washedwith water (150 mL) and saturated brine (50 mL) successively, dried overanhydrous magnesium sulfate, and then the solvent was removed underreduced pressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled referencecompound (421 mg) as a colorless oil. (Yield 69%)

¹H-NMR (500 MHz, CDCl₃) δ 3.48 (s, 3H), 3.87 (s, 3H), 5.16 (s, 2H), 6.56(dd, J = 8.8, 2.7 Hz, 1H), 6.63 (d, J = 2.7 Hz, 1H), 7.40 (d, J = 8.8Hz, 1H)

Reference Example 248-Hydroxymethyl-7-[2-methoxy-4-(2-methylbenzoyloxy)phenyl]-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 24)

7-(4-Hydroxy-2-methoxyphenyl)-8-hydroxymethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 3-5, 430 mg, 1.31 mmol) was dissolved intetrahydrofuran (10 mL), and triethylamine (365 μL, 2.62 mmol) and2-methylbenzoyl chloride (222 μL, 1.70 mmol) were added theretosuccessively. After the reaction mixture was stirred at the sametemperature for 80 minutes, the reaction mixture was diluted with ethylacetate (200 mL). The mixture was washed with water (100 mL) andsaturated brine (100 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled reference compound (362 mg) asa colorless solid. (Yield 62%)

¹H-NMR (400 MHz, CDCl₃) δ 1.40 (s, 3H), 1.50 (s, 3H), 2.06 (t, J = 4.8Hz, 1H), 2.70 (s, 3H), 3.78 (s, 1H), 3.79 (s, 3H), 4.49 (d, J = 4.8 Hz,2H), 6.70 (d, J = 8.1 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.84 (d, J =2.2 Hz, 1H), 6.90 (dd, J = 8.2, 2.2 Hz, 1H), 7.22 (d, J = 8.2 Hz, 1H),7.34 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.49-7.53 (m, 1H),8.19 (d, J = 7.6 Hz, 1H), 8.59 (s, 1H)

Reference Example 25 5-Bromothiophene-2-carbonylchloride (ReferenceCompound No. 25)

A mixture of 5-bromothiophene-2-carboxylic acid (300 mg, 1.45 mmol),thionyl chloride (423 μL, 5.80 mmol), and N,N-dimethylformamide (1 drop)was dissolved in chloroform (3 mL), and refluxed for 1 hour. Aftercooling down, the reaction mixture was concentrated under reducedpressure to give the titled reference compound (324 mg) as a pale yellowsolid. (Yield 99%)

¹H-NMR (400 MHz, CDCl₃) δ 7.19 (d, J = 4.2 Hz, 1H), 7.74 (d, J = 4.2 Hz,1H)

Examples Example 18-Benzoyloxymethyl-7-(2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 1-1)

8-Hydroxymethyl-7-(2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 3-1, 54.2 mg, 0.17 mmol) was dissolved intetrahydrofuran (1.5 mL) and triethylamine (73.0 μL, 0.52 mmol) andbenzoyl chloride (30.0 μL, 0.26 mmol) were added thereto successively.The reaction mixture was stirred at room temperature for 24 hours. Ethylacetate (30 mL) and water (30 mL) were added to the reaction mixture andpartitioned. The organic layer was washed with water (30 mL) andsaturated brine (30 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was filtered with ethyl acetate to give the titledcompound (54.1 mg) as a colorless solid. (Yield 76%)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.25 (s, 3H), 1.30 (s, 3H), 3.60 (s, 3H),4.97 (d, J = 12.5 Hz, 1H), 5.19 (d, J = 12.5 Hz, 1H), 6.20 (s, 1H), 6.66(d, J = 7.9 Hz, 1H), 6.80 (d, J = 7.9 Hz, 1H), 6.94 (td, J = 7.5, 1.0Hz, 1H), 7.03 (d, J = 8.2 Hz, 1H), 7.10 (dd, J = 7.5, 1.7 Hz, 1H), 7.31(ddd, J = 8.2, 7.5, 1.7 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.61 (t, J =7.8 Hz, 1H), 7.81 (d, J = 7.8 Hz, 2H), 9.90 (s, 1H)Using any compounds among Reference Compounds No. 3-2, 3-3, 24, and 25,the following Compounds (No. 1-2˜1-7) were obtained by a method similarto that of Compound No. 1-1.

8-Benzoyloxymethyl-7-(4-fluoro-2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 1-2)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.24 (s, 3H), 1.30 (s, 3 H), 3.60 (s, 3H),4.96 (d, J = 12.4 Hz, 1H), 5.17 (d, J = 12.4 Hz, 1H), 6.19 (s, 1H), 6.64(d, J = 8.1 Hz, 1H), 6.74 (td, J = 8.4, 2.5 Hz, 1H), 6.78 (d, J = 8.1Hz, 1H), 6.93 (dd, J = 11.5, 2.5 Hz, 1H), 7.11 (dd, J = 8.4, 7.1 Hz,1H), 7.48 (t, J = 7.8 Hz, 2H), 7.62 (t, J = 7.8 Hz, 1H), 7.81 (d, J =7.8 Hz, 2H), 9.92 (s, 1H)8-Benzoyloxymethyl-7-(5-fluoro-2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 1-3)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.23 (s, 3H), 1.30 (s, 3H), 3.58 (s, 3H),4.98 (d, J = 12.5 Hz, 1H), 5.21 (d, J = 12.5 Hz, 1H), 6.23 (s, 1H), 6.68(d, J = 8.1 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 6.96 (dd, J = 9.0, 3.2Hz, 1H), 7.02 (dd, J = 8.9, 4.6 Hz, 1H), 7.13 (td, J = 8.9, 3.2 Hz, 1H),7.48 (t, J = 7.4 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.81 (d, J = 7.4 Hz,2H), 9.94 (s, 1H) 7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(4-methoxybenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 1-4)  

¹H-NMR (400 MHz, CDCl₃) δ 1.46 (s, 6H), 2.71 (s, 3H), 3.69 (s, 3H), 3.80(s, 1H), 3.85 (s, 3H), 5.02 (d, J = 12.8 Hz, 1H), 5.33 (d, J = 12.8 Hz,1H), 6.74 (d, J = 8.2 Hz, 1H), 6.82 (d, J = 2.2 Hz, 1H), 6.83 (d, J =8.2 Hz, 1H), 6.89 (d, J = 9.0 Hz, 2H), 6.90 (dd, J = 8.1, 2.2 Hz, 1H),7.26 (d, J = 8.1 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz,1H), 7.48-7.52 (m, 1H) , 7.93 (d, J = 9.0 Hz, 2H), 8.19 (d, J = 8.0 Hz,1H), 8.65 (s, 1H) 7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(4-methylbenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro- 1H-quinoxalin-2-one(Compound No. 1-5)  

¹H-NMR (400 MHz, CDCl₃) δ 1.45 (s, 6H), 2.39 (s, 3H), 2.71 (s, 3H), 3.68(s, 3H), 3.81 (s, 1H), 5.03 (d, J = 12.8 Hz, 1H), 5.34 (d, J = 12.8 Hz,1H), 6.75 (d, J = 8.2 Hz, 1H), 6.82 (d, J = 2.0 Hz, 1H), 6.83 (d, J =8.2 Hz, 1H), 6.90 (dd, J = 8.2, 2.0 Hz, 1H), 7.21 (d, J = 8.2 Hz, 2H),7.26 (d, J = 8.2 Hz, 1H), 7.34 (d, J = 7.9 Hz, 1H), 7.35 (t, J = 7.9 Hz,1H), 7.49-7.52 (m, 1H), 7.87 (d, J = 8.2 Hz, 2H), 8.19 (d, J = 7.9 Hz,1H), 8.59 (s, 1H) 8-(3-Fluorobenzoyloxymethyl)-7-[2-methoxy-4-(2-methylbenzoyloxy)phenyl]-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 1-6)  

¹H-NMR (500 MHz, CDCl₃) δ 1.46 (s, 3H), 1.46 (s, 3H), 2.71 (s, 3H), 3.69(s, 3H), 3.82 (s, 1H), 5.07 (d, J = 12.7 Hz, 1H), 5.35 (d, J = 12.7 Hz,1H), 6.76 (d, J = 8.2 Hz, 1H), 6.83 (d, J = 2.1 Hz, 1H), 6.83 (d, J =8.2 Hz, 1H), 6.91 (dd, J = 8.2, 2.1 Hz, 1H), 7.23- 7.29 (m, 2H),7.33-7.37 (m, 2H), 7.40 (td, J = 7.8, 5.6 Hz, 1H), 7.49-7.52 (m, 1H),7.63-7.66 (m, 1H), 7.77 (d, J = 7.8 Hz, 1H), 8.19 (d, J = 7.6 Hz, 1H),8.49 (s, 1H) 8-(5-Bromothiophen-2-ylcarbonyloxymethyl)-7-[2-methoxy-4-(2-methylbenzoyloxy)phenyl]-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 1-7)  

¹H-NMR (400 MHz, CDCl₃) δ 1.45 (s, 3H), 1.46 (s, 3H), 2.71 (s, 3H), 3.71(s, 3H), 3.81 (s, 1H), 5.01 (d, J = 12.7 Hz, 1H), 5.30 (d, J = 12.7 Hz,1H), 6.75 (d, J = 8.1 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.83 (d, J =2.2 Hz, 1H), 6.91 (dd, J = 8.1, 2.2 Hz, 1H), 7.06 (d, J = 3.9 Hz, 1H),7.25 (d, J = 8.1 Hz, 1H), 7.34 (d, J = 7.7 Hz, 1H), 7.35 (t, J = 7.7 Hz,1H), 7.49-7.52 (m, 1H), 7.52 (d, J = 3.9 Hz, 1H), 8.19 (d, J = 7.7 Hz,1H), 8.47 (s, 1H)

Example 27-(5-Fluoro-2-methoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 2-1)

8-Chloromethyl-7-(5-fluoro-2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 4-2, 50.9 mg, 0.14 mmol),5-methyl-2-thiophenecarboxylyc acid (62.5 mg, 0.44 mmol), and potassiumcarbonate (79.9 mg, 0.58 mmol) were suspended in anhydrous.N,N-dimethylformamide (1.5 mL) and stirred at 80° C. for 4.5 hours.Ethyl acetate (30 mL) and water (30 mL) were added to the reactionmixture and partitioned. The organic layer was washed with water (30 mL)and saturated brine (30 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled compound (55.0 mg) as acolorless solid. (Yield 85%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.23 (s, 3H), 1.30 (s, 3H), 2.47 (s, 3H),3.60 (s, 3H), 4.90 (d, J = 12.5 Hz, 1H), 5.17 (d, J = 12.5 Hz, 1H), 6.22(s, 1H), 6.67 (d, J = 8.1 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 6.88 (d, J= 3.7 Hz, 1H), 6.94 (dd, J = 9.0, 3.2 Hz, 1H), 7.02 (dd, J = 8.9, 4.6Hz, 1H), 7.14 (td, J = 8.9, 3.2 Hz, 1H), 7.46 (d, J = 3.7 Hz, 1H), 9.86(s, 1H)Using any compounds among Reference Compounds No. 4-1˜4-3, 14-1, 14-2,and available compounds, the following Compounds (No. 2-2˜2-19) wereobtained by a method similar to that of Compound No. 2-1.

7-(5-Fluoro-2-methoxyphenyl)-8-(4-methylbenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 2-2)  

1H-NMR (400 MHz, DMSO-d₆) δ 1.23 (s, 3H), 1.30 (s, 3H), 2.35 (s, 3H),3.58 (s, 3H), 4.95 (d, J = 12.5 Hz, 1H), 5.19 (d, J = 12.5 Hz, 1H), 6.23(s, 1H), 6.67 (d, J = 8.1 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 6.95 (dd, J= 9.0, 3.2 Hz, 1H), 7.01 (dd, J = 9.0, 4.8 Hz, 1H), 7.13 (td, J = 9.0,3.2 Hz, 1H), 7.27 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 8.1 Hz, 2H), 9.92(s, 1H) 7-(5-Fluoro-2-methoxyphenyl)-8-(3-methylbenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 2-3)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.23 (s, 3H), 1.31 (s, 3H), 2.32 (s, 3H),3.59 (s, 3H), 4.97 (d, J = 12.5 Hz, 1H), 5.21 (d, J = 12.5 Hz, 1H), 6.23(s, 1H), 6.68 (d, J = 8.1 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 6.96 (dd, J= 9.0, 3.2 Hz, 1H), 7.02 (dd, J = 8.8, 4.5 Hz, 1H), 7.13 (td, J = 8.8,3.2 Hz, 1H), 7.36 (t, J = 7.8 Hz, 1H), 7.43 (d, J = 7.8 Hz, 1H),7.60-7.61 (m, 2H), 9.94 (s, 1H)7-(5-Fluoro-2-methoxyphenyl)-8-(2-methylbenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 2-4)  

¹H-NMR (400 MHz, CDCl₃) δ 1.45 (s, 6H), 2.55 (s, 3H), 3.65 (s, 3H), 3.82(s, 1H), 4.99 (d, J = 12.8 Hz, 1H), 5.32 (d, J = 12.8 Hz, 1H), 6.74 (d,J = 8.1 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 6.86 (dd, J = 8.8, 4.4 Hz,1H), 6.95 (dd, J = 8.8, 3.2 Hz, 1H), 7.04 (td, J = 8.8, 3.2 Hz, 1H),7.20-7.23 (m, 2H), 7.37-7.41 (m, 1H), 7.84 (dd, J = 8.3, 1.4 Hz, 1H),8.51 (s, 1H) 7-(5-Fluoro-2-methoxyphenyl)-8-(thiophen-2-ylcarbonyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 2-5)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.23 (s, 3H), 1.30 (s, 3H), 3.60 (s, 3H),4.93 (d, J = 12.5 Hz, 1H), 5.20 (d, J = 12.5 Hz, 1H), 6.22 (s, 1H), 6.67(d, J = 8.2 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 6.95 (dd, J = 9.1, 3.2Hz, 1H), 7.03 (dd, J = 8.9, 4.6 Hz, 1H), 7.14 (td, J = 8.9, 3.2 Hz, 1H),7.17 (dd, J = 4.9, 3.7 Hz, 1H), 7.65 (dd, J = 3.7, 1.3 Hz, 1H), 7.90(dd, J = 4.9, 1.3 Hz, 1H), 9.89 (s, 1H)7-(5-Fluoro-2-methoxyphenyl)-8-(4-methoxybenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 2-6)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.23 (s, 3H), 1.30 (s, 3H), 3.58 (s, 3H),3.81 (s, 3H), 4.94 (d, J = 12.6 Hz, 1H), 5.18 (d, J = 12.6 Hz, 1H), 6.22(s, 1H), 6.67 (d, J = 8.1 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 6.95 (dd, J= 9.0, 3.2 Hz, 1H), 7.00 (d, J = 9.0 Hz, 2H), 7.00-7.03 (m, 1H), 7.13(td, J = 8.6, 3.2 Hz, 1H), 7.76 (d, J = 9.0 Hz, 2H), 9.90 (s, 1H)7-(4-Fluoro-2-methoxyphenyl)-8-(4-methoxybenzoyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 2-7)  

¹H-NMR (400 MHz, CDCl₃) δ 1.20 (s, 3H), 1.42 (s, 3H), 3.47 (s, 3H), 3.74(s, 3H), 3.79 (s, 1H), 3.83 (s, 3H), 5.14 (d, J = 13.4 Hz, 1H), 5.28 (d,J = 13.4 Hz, 1H), 6.63-6.68 (m, 1H), 6.64 (d, J = 9.3 Hz, 1H), 6.76 (d,J = 7.8 Hz, 1H), 6.84 (d, J = 9.0 Hz, 2H), 6.82- 6.86 (m, 1H), 7.21 (t,J = 7.5 Hz, 1H), 7.78 (d, J = 9.0 Hz, 2H)7-(4-Fluoro-2-methoxyphenyl)-8-(thiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4- dihydro-1H-quinoxalin-2-one(Compound No. 2-8)  

¹H-NMR (400 MHz, CDCl₃) δ 1.20 (s, 3H), 1.42 (s, 3H), 3.46 (s, 3H), 3.75(s, 3H), 3.79 (s, 1H), 5.14 (d, J = 13.3 Hz, 1H), 5.28 (d, J = 13.3 Hz.1H), 6.65-6.69 (m, 2H), 6.76 (d, J = 8.1 Hz, 1H), 6.85 (d, J = 8.1 Hz,1H), 7.04 (dd, J = 5.0, 3.8 Hz, 1H), 7.20 (dd, J = 8.5, 6.5 Hz, 1H),7.50 (dd, J = 5.0, 1.2 Hz, 1H), 7.63 (dd, J = 3.8, 1.2 Hz, 1H)7-(4-Fluoro-2-methoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro- 1H-quinoxalin-2-one(Compound No. 2-9)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.02 (s, 3H), 1.24 (s, 3H), 2.46 (s, 3H),3.30 (s, 3H), 3.72 (s, 3H), 5.04 (d, J = 13.4 Hz, 1H), 5.21 (d, J = 13.4Hz, 1H), 6.22 (s, 1H), 6.76 (d, J = 7.9 Hz, 1H), 6.78 (td, J = 8.4, 2.4Hz, 1H), 6.83 (d, J = 7.9 Hz, 1H), 6.87 (d, J = 3.7 Hz, 1H), 6.96 (dd, J= 11.3, 2.4 Hz, 1H), 7.23 (dd, J = 8.4, 7.2 Hz, 1H), 7.38 (d, J = 3.7Hz, 1H) 7-(5-Chloro-2-methoxyphenyl)-8-(4-methoxybenzoyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 2-10)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.02 (s, 3H), 1.25 (s, 3H), 3.32 (s, 3H),3.71 (s, 3H), 3.80 (s, 3H), 5.09 (d, J = 13.4 Hz, 1H), 5.25 (d, J = 13.4Hz, 1H), 6.28 (s, 1H), 6.81 (d, J = 8.1 Hz, 1H), 6.84 (d, J = 8.1 Hz,1H), 6.96 (dt, J = 9.0, 2.5 Hz, 2H), 7.07 (d, J = 8.9 Hz, 1H), 7.26 (d,J = 2.7 Hz, 1H), 7.36 (dd, J = 8.9, 2.7 Hz, 1H), 7.66 (dt, J = 9.0, 2.5Hz, 2H) 7-(5-Chloro-2-methoxyphenyl)-8-(thiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 2-11)  

¹H-NMR (400 MHz, CDCl₃) δ 1.23 (s, 3H), 1.42 (s, 3H), 3.45 (s, 3H), 3.75(s, 3H), 3.82 (s, 1H), 5.14 (d, J = 13.3 Hz, 1H), 5.30 (d, J = 13.3 Hz,1H), 6.77 (d, J = 8.1 Hz, 1H), 6.83-6.87 (m, 1H), 6.86 (d, J = 8.1 Hz,1H), 7.04 (dd, J = 5.0, 3.7 Hz, 1H), 7.23-7.29 (m, 2H), 7.51 (dd, J =5.0, 1.2 Hz, 1H), 7.63 (dd, J = 3.7, 1.2 Hz, 1H)7-(5-Chloro-2-methoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro- 1H-quinoxalin-2-one(Compound No. 2-12)  

¹H-NMR (400 MHz, CDCl₃) δ 1.24 (s, 3H), 1.41 (s, 3H), 2.48 (s, 3H), 3.44(s, 3H), 3.75 (s, 3H), 3.81 (s, 1H), 5.09 (d, J = 13.2 Hz, 1H), 5.27 (d,J = 13.2 Hz, 1H), 6.70 (d, J = 3.8 Hz, 1H), 6.76 (d, J = 8.0 Hz, 1H),6.83-6.87 (m, 1H), 6.86 (d, J = 8.0 Hz, 1H), 7.23- 7.26 (m, 2H), 7.43(d, J = 3.8 Hz, 1H)7-(2-Methoxy-4-methoxymethoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 2-13)  

¹H-NMR(500 MHz, CDCl₃) δ 1.44 (s, 6H), 2.51 (s, 3H), 3.53 (s, 3H), 3.68(s, 3H), 3.76 (s, 1H), 4.98 (d, J = 12.5 Hz, 1H), 5.22 (d, J = 6.7 Hz,1H), 5.23 (d, J = 6.7 Hz, 1H), 5.26 (d, J = 12.5 Hz, 1H), 6.64 (d, J =2.3 Hz, 1H), 6.71 (dd, J = 8.2, 2.3 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H),6.74 (d, J = 3.7 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 7.11 (d, J = 8.2 Hz,1H), 7.58 (d, J = 3.7 Hz, 1H), 8.48 (s, 1H)7-(5-Chloro-2-methoxyphenyl)-8-(5-chlorothiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 2-14)   

¹H-NMR (500 MHz, CDCl₃) δ 1.25 (s, 3H), 1.42 (s, 3H), 3.43 (s, 3H), 3.75(s, 3H), 3.83 (s, 1H), 5.12 (d, J = 13.1 Hz, 1H), 5.28 (d, J = 13.1 Hz,1H), 6.77 (d, J = 8.3 Hz, 1H), 6.85 (d, J = 8.3 Hz, 1H), 6.86 (d, J =7.6 Hz, 1H), 6.87 (d, J = 4.0 Hz, 1H), 7.22-7.27 (m, 2H), 7.40 (d, J =4.0 Hz, 1H) 7-(5-Chloro-2-methoxyphenyl)-8-(5-ethylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 2-15)

¹H-NMR (400 MHz, CDCl₃) δ 1.25 (s, 3H), 1.29 (t, J = 7.6 Hz, 3H), 1.41(s, 3H), 2.83 (q, J = 7.6 Hz, 2H), 3.44 (s, 3H), 3.75 (s, 3H), 3.81 (s,1H), 5.09 (d, J = 13.2 Hz, 1H), 5.28 (d, J = 13.2 Hz, 1H), 6.74 (d, J =3.7 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.84 (d, J = 9.5 Hz, 1H), 6.86(d, J = 8.1 Hz, 1H), 7.23-7.26 (m, 2H), 7.46 (d, J = 3.7 Hz, 1H)8-(5-Bromothiophen-2-ylcarbonyloxymethyl)-7-(4-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2- one(Compound No. 2-16)  

¹H-NMR (400 MHz, CDCl₃) δ 1.23 (s, 3H), 1.42 (s, 3H), 3.44 (s, 3H), 3.75(s, 3H), 3.80 (s, 1H), 5.11 (d, J = 13.2 Hz, 1H), 5.27 (d, J = 13.2 Hz,1H), 6.64-6.70 (m, 2H), 6.76 (d, J = 8.1 Hz, 1H), 6.84 (d, J = 8.1 Hz,1H), 7.01 (d, J = 3.9 Hz, 1H), 7.17-7.21 (m, 1H), 7.37 (d, J = 3.9 Hz,1H) 8-(4-Chlorobenzoyloxymethyl)-7-(5-chloro-2-methoxyphenyl)-1,3,3-trimethy1-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 2-17)  

¹H-NMR (500 MHz, CDCl₃) δ 1.23 (s, 3H), 1.41 (s, 3H), 3.44 (s, 3H), 3.74(s, 3H), 3.82 (s, 1H), 5.16 (d, J = 13.3 Hz, 1H), 5.34 (d, J = 13.3 Hz,1H), 6.77 (d, J = 8.0 Hz, 1H), 6.83 (d, J = 9.4 Hz, 1H), 6.87 (d, J =8.0 Hz, 1H), 7.22-7.26 (m, 2H), 7.35 (d, J = 8.9 Hz, 2H), 7.75 (d, J =8.9 Hz, 2H) 7-(5-Chloro-2-methoxyphenyl)-8-(5-methoxyfuran-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 2-18)  

¹H-NMR (500 MHz, CDCl₃) δ 1.25 (s, 3H), 1.40 (s, 3H), 3.43 (s, 3H), 3.75(s, 3H), 3.80 (s, 1H), 3.90 (s, 3H), 5.07 (d, J = 13.3 Hz, 1H), 5.23 (d,J = 13.3 Hz, 1H), 5.26 (d, J = 3.7 Hz, 1H), 6.75 (d, J = 7.9 Hz, 1H),6.82-6.75 (m, 1H), 6.84 (d, J = 7.9 Hz, 1H), 6.93 (d, J = 3.7 Hz, 1H),7.24-7.26 (m, 2H) 7-(4-Fluoro-2-methoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 2-19)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.24 (s, 3H), 1.30 (s, 3H), 2.48 (s, 3H),3.63 (s, 3H), 4.88 (d, J = 12.5 Hz, 1H), 5.13 (d, J = 12.5 Hz, 1H), 6.19(s, 1H), 6.63 (d, J = 8.1 Hz, 1H), 6.77 (td, J = 8.4, 2.4 Hz, 1H), 6.78(d, J = 8.1 Hz, 1H), 6.89 (d, J = 3.8 Hz, 1H) , 6.94 (dd, J = 11.5, 2.4Hz, 1H), 7.10 (dd, J = 8.4, 7.1 Hz, 1H), 7.47 (d, J = 3.8 Hz, 1H), 9.84(s, 1H)

Example 37-(4-Fluoro-2-methoxyphenyl)-8-phenoxymethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 3-1)

A mixture of8-chloromethyl-7-(4-fluoro-2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 4-1, 47.1 mg, 0.14 mmol), phenol (37.5 mg, 0.40mmol), and potassium carbonate (73.0 mg, 0.53 mmol) was suspended inanhydrous N,N-dimethylformamide (1.5 mL) and stirred at 80° C. for 19hours. After cooling down, ethyl acetate (30 mL) and water (30 mL) wereadded to the reaction mixture and partitioned. The organic layer waswashed with water (30 mL) and saturated brine (30 mL) successively,dried over anhydrous magnesium sulfate, and then the solvent was removedunder reduced pressure. The obtained residue was purified by silica gelcolumn chromatography (hexane-ethyl acetate) to give the titled compound(35.7 mg) as a pale yellow solid. (Yield 67%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.18 (s, 3H), 1.27 (s, 3H), 3.68 (s, 3H),4.62 (d, J = 11.5 Hz, 1H), 5.11 (d, J = 11.5 Hz, 1H), 6.14 (s, 1H), 6.63(d, J = 8.1 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.71-6.77 (m, 3H), 6.87(t, J = 7.3 Hz, 1H), 6.93 (dd, J = 11.4, 2.6 Hz, 1H), 7.12 (dd, J = 8.3,7.1 Hz, 1H), 7.19 (dd, J = 8.5, 7.3 Hz, 2H), 9.50 (s, 1H)Using any compounds among Reference Compounds No. 4-2, 14-1, 14-2, andavailable compounds, the following Compounds (No. 3-2˜3-19) wereobtained by a method similar to that of Compound No. 3-1.

7-(5-Fluoro-2-methoxyphenyl)-8-phenoxymethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 3-2)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.19 (s, 3H), 1.28 (s, 3H), 3.65 (s, 3H),4.62 (d, J = 11.5 Hz, 1H), 5.15 (d, J = 11.5 Hz, 1H), 6.18 (s, 1H), 6.67(d, J = 8.1 Hz, 1H), 6.73 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.1 Hz, 1H),6.87 (t, J = 7.3 Hz, 1H), 6.94 (dd, J = 9.3, 3.2 Hz, 1H), 7.01 (dd, J =8.9, 4.9 Hz, 1H), 7.11 (td, J = 8.9, 3.2 Hz, 1H), 7.19 (dd, J = 8.8, 7.3Hz, 2H), 9.56 (s, 1H) 7-(5-Fluoro-2-methoxyphenyl)-8-(3-fluorophenoxymethyl)-3,3-dimethyl- 3,4-dihydro-1H-quinoxalin-2-one(Compound No. 3-3)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.19 (s, 3H), 1.28 (s, 3H), 3.64 (s, 3H),4.63 (d, J = 11.6 Hz, 1H), 5.15 (d, J = 11.6 Hz, 1H), 6.19 (s, 1H),6.56-6.59 (m, 2H), 6.67 (d, J = 8.2 Hz, 1H), 6.68- 6.72 (m, 1H) , 6.76(d, J = 8.2 Hz, 1H), 6.93 (dd, J = 9.2, 3.1 Hz, 1H), 7.01 (d d, J = 8.8,4.7 Hz, 1H), 7.11 (td, J = 8.8, 3.1 Hz, 1H), 7.19-7.24 (m, 1H), 9.66 (s,1H) 7-(5-Fluoro-2-methoxyphenyl)-8-(4-methylphenoxymethyl)-3,3-dimethyl- 3,4-dihydro-1H-quinoxalin-2-one(Compound No. 3-4)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.18 (s, 3H), 1.28 (s, 3H), 2.18 (s, 3H),3.64 (s, 3H), 4.58 (d, J = 11.7 Hz, 1H), 5.12 (d, J = 11.7 Hz, 1H), 6.17(s, 1H), 6.61 (d, J = 8.7 Hz, 2H), 6.66 (d, J = 8.1 Hz, 1H), 6.74 (d, J= 8.1 Hz, 1H), 6.93 (dd, J = 9.3, 3.2 Hz, 1H), 6.98 (d, J = 8.7 Hz, 2H),7.01 (dd, J = 9.0, 4.9 Hz, 1H), 7.11 (td, J = 9.0, 3.2 Hz, 1H), 9.48 (s,1H) 7-(5-Fluoro-2-methoxyphenyl)-8-(3-methylphenoxymethyl)-3,3-dimethyl- 3,4-dihydro-1H-quinoxalin-2-one(Compound No. 3-5)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.18 (s, 3H), 1.28 (s, 3H), 2.19 (s, 3H),3.66 (s, 3H), 4.61 (d, J = 11.9 Hz, 1H), 5.16 (d, J = 11.9 Hz, 1H), 6.17(s, 1H), 6.50-6.60 (m, 1H), 6.52 (s, 1H), 6.65- 6.78 (m, 1H), 6.66 (d, J= 8.1 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.94 (dd, J = 9.2, 3.2 Hz, 1H),7.01- 7.08 (m, 2H), 7.13 (td, J = 8.7, 3.2 Hz, 1H), 9.49 (s, 1H)7-(5-Fluoro-2-methoxyphenyl)-8- (2-methylphenoxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 3-6)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.17 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H),3.66 (s, 3H), 4.67 (d, J = 11.7 Hz, 1H), 5.17 (d, J = 11.7 Hz, 1H), 6.19(s, 1H), 6.61 (d, J = 7.8 Hz, 1H), 6.68 (d, J = 8.1 Hz, 1H), 6.74-6.78(m, 1H) , 6.76 (d, J = 8.1 Hz, 1H), 6.96 (dd, J = 9.0, 3.2 Hz, 1H),6.99-7.09 (m, 3H), 7.13 (td, J = 8.7, 3.2 Hz, 1H), 9.61 (s, 1H)7-(4-Fluoro-2-methoxyphenyl)-8-(2-methyl-5-nitrophenoxymethyl)-1,3,3-trimethyl-3,4- dihydro-1H-quinoxalin-2-one(Compound No. 3-7)  

¹H-NMR (400 MHz, DMSO-d₆) δ 0.53 (s, 3H), 1.18 (s, 3H), 2.09 (s, 3H),3.37 (s, 3H), 3.83 (s, 3H), 4.89 (d, J = 14.2 Hz, 1H), 5.47 (d, J = 14.2Hz, 1H), 6.13 (s, 1H), 6.78 (d, J = 8.1 Hz, 1H), 6.82 (d, J = 8.1 Hz,1H), 6.92 (td, J = 8.4, 2.4 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 7.03 (dd,J = 11.5, 2.4 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H), 7.42 (dd, J = 8.4, 7.0Hz, 1H), 7.60 (dd, J = 8.2, 2.2 Hz, 1H)7-(5-Chloro-2-methoxyphenyl)-8-(2-methyl-5-nitrophenoxymethyl)-1,3,3-trimethyl-3,4- dihydro-1H-quinoxalin-2-one(Compound No. 3-8)  

¹H-NMR (400 MHz, DMSO-d₆) δ 0.54 (s, 3H), 1.18 (s, 3H), 2.09 (s, 3H),3.37 (s, 3H), 3.81 (s, 3H), 4.88 (d, J = 14.2 Hz, 1H), 5.48 (d, J = 14.2Hz, 1H), 6.19 (s, 1H), 6.79 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 8.1 Hz,1H), 6.99 (d, J = 2.4 Hz, 1H), 7.13 (d, J = 9.7 Hz, 1H), 7.30 (d, J =8.2 Hz, 1H), 7.43 (dd, J = 9.7, 2.4 Hz, 1H), 7.43 (d, J = 2.3 Hz, 1H),7.61 (dd, J = 8.2, 2.3 Hz, 1H) 7-(5-Chloro-2-methoxyphenyl)-8-(2,5-dimethylphenoxymethyl)-1,3,3-trimethyl-3,4- dihydro-1H-quinoxalin-2-one(Compound No. 3-9)  

¹H-NMR (500 MHz, DMSO-d₆) δ 0.80 (s, 3H), 1.16 (s, 3H), 1.91 (s, 3H),2.10 (s, 3H), 3.32 (s, 3H), 3.80 (s, 3H), 4.72 (d, J = 13.8 Hz, 1H),5.19 (d, J = 13.8 Hz, 1H), 6.13 (s, 1H), 6.16 (s, 1H), 6.49 (d, J = 7.6Hz, 1H), 6.79 (d, J = 7.9 Hz, 1H), 6.82 (d, J = 7.9 Hz, 1H), 6.86 (d, J= 7.6 Hz, 1H), 7.14 (d, J = 9.0 Hz, 1H), 7.31 (d, J = 2.7 Hz, 1H), 7.42(d, J = 9.0, 2.7 Hz, 1H) 7-(5-Chloro-2-methoxyphenyl)-8-[2-(2-hydroxyethyl)phenoxymethyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 3-10)  

¹H-NMR (500 MHz, CDCl₃) δ 1.13 (s, 3H), 1.39 (s, 3H), 2.01 (t, J = 6.0Hz, 1H), 2.67-2.71 (m, 1H), 2.76- 2.80 (m, 1H), 3.42 (s, 3H), 3.68-3.72(m, 2H), 3.79 (s, 4H), 4.83 (d, J = 12.8 Hz, 1H), 5.14 (d, J = 12.8 Hz,1H), 6.47 (d, J = 7.7 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.81 (t, J =7.7 Hz, 1H), 6.89 (d, J = 8.1 Hz, 1H), 6.89 (d, J = 8.7 Hz, 1H), 7.03(t, J = 7.7 Hz, 1H), 7.08 (d, J = 7.7 Hz, 1H), 7.28 (d, J = 2.7 Hz, 1H),7.30 (d, J = 8.7, 2.7 Hz, 1H) 7-(5-Chloro-2-methoxyphenyl)-8-(3-trifluoromethylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 3-11)  

¹H-NMR (500 MHz, CDCl₃) δ 0.90 (s, 3H), 1.29 (s, 3H), 3.51 (s, 3H), 3.73(s, 1H), 3.79 (s, 3H), 4.84 (d, J = 13.3 Hz, 1H), 5.23 (d, J = 13.3 Hz,1H), 6.71 (br s, 1H), 6.72 (d, J = 8.3 Hz, 1H), 6.78 (dd, J = 8.1, 2.4Hz, 1H), 6.86-6.88 (m, 1H), 6.87 (d, J = 8.3 Hz, 1H), 7.06 (d, J = 7.6Hz, 1H), 7.21 (t, J = 8.1 Hz, 1H), 7.27-7.30 (m, 2H)7-(5-Chloro-2-methoxyphenyl)-8-(4- phenylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 3-12)  

¹H-NMR (400 MHz, CDCl₃) δ 1.02 (s, 3H), 1.30 (s, 3H) , 3.51 (s, 3H),3.74 (s, 1H), 3.80 (s, 3H), 4.82 (d, J = 12.9 Hz, 1H), 5.18 (d, J = 12.9Hz, 1H), 6.65 (d, J = 8.7 Hz, 2H), 6.72 (d, J = 7.8 Hz, 1H), 6.87 (d, J= 7.8 Hz, 1H), 6.88 (d, J = 8.7 Hz, 1H), 7.26-7.39 (m, 7H), 7.44-7.49(m, 2H) 7-(5-Chloro-2-methoxyphenyl)-8-(2-methoxyphenoxymethyl)-1,3,3-trimethyl-3,4- dihydro-1H-quinoxalin-2-one(Compound No. 3-13)  

¹H-NMR (400 MHz, CDCl₃) δ 1.06 (s, 3H), 1.30 (s, 3H), 3.52 (s, 3H), 3.72(s, 1H), 3.74 (s, 3H), 3.77 (s, 3H), 4.80 (d, J = 12.7 Hz, 1H), 5.21 (d,J = 12.7 Hz, 1H), 6.40 (dd, J = 8.0, 1.3 Hz, 1H), 6.65-6.69 (m, 1H),6.71 (d, J = 8.0 Hz, 1H), 6.75-6.80 (m, 2H), 6.83 (d, J = 8.0 Hz, 1H),6.85 (d, J = 8.8 Hz, 1H), 7.25-7.30 (m, 2H)7-(5-Chloro-2-methoxyphenyl)-8-(3- methoxycarbonylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2- one (Compound No. 3-14)  

¹H-NMR (500 MHz, CDCl₃) δ 0.89 (s, 3H), 1.34 (s, 3H), 3.50 (s, 3H), 3.73(s, 1H), 3.78 (s, 3H), 3.90 (s, 3H), 4.82 (d, J = 13.0 Hz, 1H), 5.23 (d,J = 13.0 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 6.84 (ddd, J = 8.0, 2.5, 1.2Hz, 1H), 6.85 (d, J = 8.7 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 7.14 (dd, J= 2.5, 1.2 Hz, 1H), 7.18 (t, J = 8.0 Hz, 1H), 7.27 (dd, J = 8.7, 2.6 Hz,1H), 7.37 (d, J = 2.6 Hz, 1H), 7.51 (dt, J = 8.0, 1.2 Hz, 1H)8-(5-Chloro-2-methylphenoxymethyl)-7-(4-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4- dihydro-1H-quinoxalin-2-one(Compound No. 3-15)  

¹H-NMR (500 MHz, CDCl₃) δ 0.90 (s, 3H), 1.32 (s, 3H), 2.02 (s, 3H), 3.46(s, 3H), 3.72 (s, 1H), 3.82 (s, 3H), 4.80 (d, J = 13.6 Hz, 1H), 5.21 (d,J = 13.6 Hz, 1H), 6.26 (d, J = 1.8 Hz, 1H), 6.68 (dd, J = 7.9, 1.8 Hz,1H), 6.71-6.73 (m, 1H), 6.72 (d, J = 8.1 Hz, 1H), 6.77 (td, J = 8.2, 2.4Hz, 1H), 6.86 (d, J = 8.1 Hz, 1H), 6.89 (d, J = 7.9 Hz, 1H), 7.30 (dd, J= 8.2, 6.7 Hz, 1H) 7-(4-Fluoro-2-methoxyphenyl)-8-(2-methoxy-5-nitrophenoxymethyl)-1,3,3-trimethyl-3,4-dihydro- 1H-quinoxalin-2-one(Compound No. 3-16)  

¹H-NMR (400 MHz, DMSO-d₆) δ 0.70 (s, 3H), 1.15 (s, 3H), 3.36 (s, 3H),3.78 (s, 3H), 3.79 (s, 3H), 4.81 (d, J = 13.6 Hz, 1H), 5.39 (d, J = 13.6Hz, 1H), 6.11 (s, 1H), 6.78 (s, 2H), 6.84 (t d, J = 8.4, 2.5 Hz, 1H),6.98 (d, J = 11.5, 2.5 Hz, 1H), 7.04 (d, J = 9.0 Hz, 1H), 7.10 (d, J =2.7 Hz, 1H), 7.34 (dd, J = 8.4, 7.1 Hz, 1H), 7.76 (dd, J = 9.0, 2.7 Hz,1H) 8-(2-Allylphenoxymethyl)-7-(4-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 3-17)  

¹H-NMR (500 MHz, CDCl₃) δ 1.05 (s, 3H), 1.33 (s, 3H), 3.19 (dd, J =15.4, 6.7 Hz, 1H), 3.26 (dd, J = 15.4, 6.7 Hz, 1H), 3.44 (s, 3H), 3.73(s, 1H), 3.79 (s, 3H), 4.79 (d, J = 12.8 Hz, 1H), 4.95-4.99 (m, 2H),5.14 (d, J = 12.8 Hz, 1H), 5.87 (ddt, J = 16.8, 10.4, 6.7 Hz, 1H), 6.40(dd, J = 7.7, 1.2 Hz, 1H), 6.68 (dd, J = 10.4, 2.5 Hz, 1H), 6.72 (dd, J= 8.2, 2.5 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H), 6.77 (td, J = 7.7, 1.3 Hz,1H), 6.85 (d, J = 7.9 Hz, 1H), 6.97 (td, J = 7.7, 1.2 Hz, 1H), 7.03 (dd,J = 7.7, 1.3 Hz, 1H), 7.25 (dd, J = 8.2, 7.0 Hz, 1H)8-(3-Acetylphenoxymethyl)-7-(4-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 3-18)  

¹H-NMR (500 MHz, DMSO-d₆) δ 0.78 (s, 3H), 1.12 (s, 3H), 2.46 (s, 3H),3.35 (s, 3H), 3.78 (s, 3H), 4.78 (d, J = 13.1 Hz, 1H), 5.22 (d, J = 13.1Hz, 1H), 6.11 (s, 1H), 6.78 (s, 2H), 6.81 (t d, J = 8.3, 2.5 Hz, 1H),6.82 (dd, J = 8.2, 2.6 Hz, 1H), 6.97 (dd, J = 11.3, 2.5 Hz, 1H),7.02-7.03 (m, 1H), 7.27 (t, J = 8.2 Hz, 1H), 7.35 (dd, J = 8.3, 7.0 Hz,1H), 7.41-7.43 (m, 1H) 8-(3-Cyanophenoxymethyl)-7-(4-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro- 1H-quinoxalin-2-one(Compound No. 3-19)  

¹H-NMR (500 MHz, DMSO-d₆) δ 0.90 (s, 3H), 1.04 (s, 3H), 3.33 (s, 3H),3.79 (s, 3H), 4.83 (d, J = 13.4 Hz, 1H), 5.17 (d, J = 13.4 Hz, 1H), 6.15(s, 1H), 6.77-6.82 (m, 3H), 6.89-6.91 (m, 1H), 6.94-6.95 (m, 1H), 6.98(dd, J = 11.3, 2.4 Hz, 1H), 7.24-7.28 (m, 2H), 7.32-7.35 (m, 1H)

Example 47-(5-Fluoro-2-methoxyphenyl)-8-(4-methylphenylaminomethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 4-1)

A mixture of8-chloromethyl-7-(5-fluoro-2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 4-2, 50.7 mg, 0.15 mmol), 4-methylaniline (19.3mg, 0.18 mmol), and potassium carbonate (60.6 mg, 0.44 mmol) wassuspended in anhydrous N,N-dimethylformamide (1 mL) and stirred at 80°C. overnight. After cooling down, ethyl acetate (30 mL) and water (30mL) were added and partitioned. The organic layer was washed with water(30 mL) and saturated brine (30 mL) successively, dried over anhydrousmagnesium sulfate, and then the solvent was removed under reducedpressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled compound (48.2mg) as a pale yellow solid. (Yield 80%)

¹H-NMR (400 MHz, CDCl₃) δ 1.38 (s, 3H), 1.49 (s, 3H), 2.25 (s, 3H), 3.65(s, 4H), 3.78 (s, 1H), 3.84 (d, J = 12.7 Hz, 1H), 4.07 (dd, J = 10.9,7.0 Hz, 1H), 6.59 (d, J = 8.1 Hz, 2H), 6.70 (d, J = 8.1 Hz, 1H), 6.75(dd, J = 9.5, 3.9 Hz, 1H), 6.75 (d, J = 8.1 Hz, 1H), 6.89-6.98 (m, 2H),7.00 (d, J = 8.1 Hz, 2H), 8.96 (s, 1H)Using any compounds among Reference Compounds No. 4-2, 14-1, 14-2, andavailable compounds, the following Compounds (No. 4-2˜4-11) wereobtained by a method similar to that of Compound No. 4-1.

7-(5-Fluoro-2-methoxyphenyl)-8- phenylaminomethyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 4-2)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.21 (s, 3H), 1.26 (s, 3H), 3.67 (s, 3H),3.84 (dd, J = 13.0, 4.9 Hz, 1H), 4.05 (dd, J = 13.0, 4.9 Hz, 1H), 5.52(t, J = 4.9 Hz, 1H), 6.13 (s, 1H), 6.55 (d, J = 8.6 Hz, 2H), 6.56 (t, J= 8.2 Hz, 1H), 6.66 (d, J = 8.1 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H),6.99-7.04 (m, 4H), 7.11 (td, J = 8.6, 3.3 Hz, 1H), 9.28 (s, 1H)7-(5-Fluoro-2-methoxyphenyl)-8-(3-methylphenylaminomethyl)-3,3-dimethyl- 3,4-dihydro-1H-quinoxalin-2-one(Compound No. 4-3)  

¹H-NMR (500 MHz, CDCl₃) δ 1.38 (s, 3H), 1.49 (s, 3H), 2.27 (s, 3H), 3.66(s, 3H), 3.72 (d, J = 11.9 Hz, 1H), 3.79 (s, 1H), 3.86 (d, J = 11.9 Hz,1H), 4.06-4.12 (m, 1H), 6.48 (d, J = 7.6 Hz, 1H), 6.49 (s, 1H), 6.63 (d,J = 7.6 Hz, 1H), 6.70 (d, J = 8.2 Hz, 1H), 6.73- 6.79 (m, 1H), 6.75 (d,J = 8.2 Hz, 1H), 6.91 (dd, J = 8.7, 3.2 Hz, 1H), 6.96 (td, J = 8.7, 3.2Hz, 1H), 7.07 (t, J = 7.6 Hz, 1H), 8.85 (s, 1H)7-(5-Fluoro-2-methoxyphenyl)-8-(2-methylphenylaminomethyl)-3,3-dimethyl- 3,4-dihydro-1H-quinoxalin-2-one(Compound No. 4-4)  

¹H-NMR (500 MHz, CDCl₃) δ 1.38 (s, 3H), 1.50 (s, 3H), 2.15 (s, 3H), 3.58(d, J = 5.2 Hz, 1H),3.61 (s, 3H), 3.80 (br s, 1H), 3.91 (d, J = 12.2 Hz,1H), 4.08-4.11 (m, 1H), 6.64 (d, J = 7.9 Hz, 1H), 6.72 (d, J = 7.9 Hz,1H), 6.76-6.79 (m, 3H), 6.92 (dd, J = 8.7, 3.2 Hz, 1H), 6.97 (td, J =8.4, 3.2 Hz, 1H), 7.09 (d, J = 7.3 Hz, 1H), 7.12 (t, J = 7.9 Hz, 1H),8.86 (s, 1H) 7-(4-Fluoro-2-methoxyphenyl)-8-(2-methoxy-5-methylphenylaminomethyl)- 1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 4-5)  

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.43 (s, 3H), 2.17 (s, 3H), 3.47(s, 3H), 3.70 (s, 3H), 3.73 (s, 1H), 3.78 (s, 3H), 4.07 (br s, 2H), 4.44(br s, 1H), 6.14 (d, J = 1.5 Hz, 1H), 6.36 (dd, J = 8.1, 1.5 Hz, 1H),6.55 (d, J = 8.1 Hz, 1H), 6.62-6.71 (m, 2H), 6.69 (d, J = 7.9 Hz, 1H),6.77 (d, J = 7.9 Hz, 1H), 7.12 (dd, J = 8.3, 6.8 Hz, 1H)7-(5-Chloro-2-methoxyphenyl)-8-(2- methoxy-5-methylphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H- quinoxalin-2-one (Compound No. 4-6)  

¹H-NMR (500 MHz, CDCl₃) δ 1.18 (s, 3H), 1.43 (s, 3H), 2.17 (s, 3H), 3.48(s, 3H), 3.71 (s, 3H), 3.75 (s, 1H), 3.77 (s, 3H), 4.10-4.14 (m, 2H),4.42-4.44 (m, 1H), 6.14 (d, J = 1.5 Hz, 1H), 6.36 (dd, J = 8.0, 1.5 Hz,1H), 6.55 (d, J = 8.0 Hz, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.78 (d, J =8.0 Hz, 1H), 6.82 (d, J = 8.9 Hz, 1H), 7.17 (d, J = 2.8 Hz, 1H), 7.25(dd, J = 8.9, 2.8 Hz, 1H) 7-(5-Chloro-2-methoxyphenyl)-8-(5-fluoro-2-methylphenylaminomethyl)- 1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 4-7)  

¹H-NMR (400 MHz, CDCl₃) δ 1.22 (s, 3H), 1.40 (s, 3H), 1.85 (s, 3H), 3.42(s, 3H), 3.73-3.80 (m, 2H), 3.77 (s, 3H), 4.10-4.22 (m, 2H), 6.03 (d, J= 11.5, 2.5 Hz, 1H), 6.24 (td, J = 8.3, 2.5, 1H), 6.72 (d, J = 8.1 Hz,1H), 6.77 (d, J = 8.1 Hz, 1H), 6.84-6.88 (m, 1H), 6.87 (d, J = 8.8 Hz,1H), 7.18 (d, J = 2.7 Hz, 1H), 7.29 (d, J = 8.8, 2.7 Hz, 1H)7-(5-Chloro-2-methoxyphenyl)-8-(2- methoxyphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2- one (Compound No. 4-8)  

¹H-NMR (500 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 3.46 (s, 3H), 3.74(s, 3H), 3.75 (s, 1H), 3.77 (s, 3H), 4.11-4.14 (m, 2H), 4.43 (br s, 1H),6.32 (dd, J = 7.8, 1.5 Hz, 1H), 6.57 (td, J = 7.8, 1.5 Hz, 1H), 6.66(dd, J = 7.8, 1.5 Hz, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.72 (td, J = 7.8,1.5 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 8.9 Hz, 1H), 7.16(d, J = 2.7 Hz, 1H), 7.24 (dd, J = 8.9, 2.7 Hz, 1H)7-(5-Chloro-2-methoxyphenyl)-8-(2,5- dimethylphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2- one (Compound No. 4-9)  

¹H-NMR (400 MHz, CDCl₃) δ 1.20 (s, 3H), 1.43 (s, 3H), 1.88 (s, 3H), 2.21(s, 3H), 3.46 (s, 3H), 3.69 (s, 1H), 3.77 (s, 3H), 4.10-4.19 (m, 2H),6.19 (s, 1H), 6.40 (d, J = 7.3 Hz, 1H), 6.71 (d, J = 7.8 Hz, 1H), 6.80(d, J = 7.8 Hz, 1H), 6.82- 6.85 (m, 1H), 6.86 (d, J = 8.8 Hz, 1H), 7.20(d, J = 2.5 Hz, 1H), 7.27 (dd, J = 8.8, 2.5 Hz, 1H)7-(5-Chloro-2-methoxyphenyl)-8-(2- isopropylphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2- one (Compound No. 4-10)  

¹H-NMR (400 MHz, CDCl₃) δ 1. 21 (d, J = 6.8 Hz, 3H), 1.15 (d, J = 6.8Hz, 3H), 1.26 (s, 3H), 1.41 (s, 3H), 2.49-2.56 (m, 1H), 3.45 (s, 3H),3.76 (s, 3H), 3.80 (s, 1H), 3.81 (br s, 1H), 4.15-4.22 (m, 2H), 6.43(dd, J = 7.4, 1.3 Hz, 1H), 6.68 (td, J = 7.4, 1.3 Hz, 1H), 6.72 (d, J =7.9 Hz, 1H), 6.81 (d, J = 7.9 Hz, 1H), 6.85 (d, J = 8.7 Hz, 1H), 7.01(td, J = 7.4, 1.3 Hz, 1H), 7.06 (dd, J = 7.4, 1.3 Hz, 1H), 7.20 (d, J =2.7 Hz, 1H), 7.26 (d, J = 8.7, 2.7 Hz, 1H)7-(4-Fluoro-2-methoxyphenyl)-8-(2- methoxyphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2- one (Compound No. 4-11)  

¹H-NMR (500 MHz, CDCl₃) δ 1.18 (s, 3H), 1.42 (s, 3H), 3.46 (s, 3H), 3.73(s, 3H), 3.76 (s, 1H), 3.77 (s, 3H), 4.10 (d, J = 5.2 Hz, 2H), 4.45 (t,J = 5.2 Hz, 1H), 6.32 (dd, J = 7.7, 1.4 Hz, 1H), 6.57 (td, J = 7.7, 1.4Hz, 1H), 6.62-6.69 (m, 3H), 6.69 (d, J = 7.9 Hz, 1H), 6.73 (td, J = 7.7,1.4 Hz, 1H), 6.78 (d, J = 7.9 Hz, 1H), 7.12 (dd, J = 8.4, 6.9 Hz, 1H)

Example 58-Benzoyloxymethyl7-(5-fluoro-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 5-1)

A mixture of8-benzoyloxymethyl-7-(5-fluoro-2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 1-3, 42.9 mg, 0.099 mmol), methyliodide (30.7 μL, 0.49mmol), and cessium carbonate (89.0 mg, 0.27 mmol) was suspended inanhydrous N,N-dimethylformamide (1 mL) and stirred at room temperaturefor 1.5 hours. The reaction mixture was diluted with ethyl acetate (100mL). The mixture was washed with water (100 mL) and saturated brine (50mL) successively, dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. The obtained residue waspurified by silica gel column chromatography (hexane-ethyl acetate) togive the titled compound (35.0 mg) as a colorless amorphous product.(Yield 79%)

¹H-NMR (400 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 3.47 (s, 3H), 3.72(s, 3H), 3.82 (br s, 1H), 5.20 (d, J = 13.3 Hz, 1H), 5.36 (d, J = 13.3Hz, 1H), 6.77 (d, J = 8.1 Hz, 1H), 6.83 (dd, J = 8.8, 4.4 Hz, 1H), 6.88(d, J = 8.1 Hz, 1H), 6.96-7.02 (m, 2H), 7.36 (t, J = 7.7 Hz, 2H),7.49-7.53 (m, 1H), 7.81-7.84 (m, 2H)Using any compounds among Reference Compounds No. 1-4˜1-7, 2-1˜2-6,2-13, 3-1˜3-6, 4-1˜4-4, 22, and available compounds, the followingCompounds (No. 5-2˜5-25) were obtained by a method similar to that ofCompound No. 5-1.

7-(5-Fluoro-2-methoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin- 2-one(Compound No. 5-2)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.02 (s, 3H), 1.25 (s, 3H), 2.45 (s, 3H),3.31 (s, 3H), 3.69 (s, 3H), 5.08 (d, J = 13.4 Hz, 1H), 5.24 (d, J = 13.4Hz, 1H), 6.26 (s, 1H), 6.80 (d, J = 7.9 Hz, 1H), 6.84 (d, J = 7.9 Hz,1H), 6.86 (d, J = 3.7 Hz, 1H), 7.05 (dd, J = 8.8, 4.6 Hz, 1H), 7.07 (dd,J = 8.9, 3.3 Hz, 1H), 7.16 (td, J = 8.8, 3.3 Hz, 1H), 7.38 (d, J = 3.7Hz, 1H) 7-(5-Fluoro-2-methoxyphenyl)-8-(4-methylbenzoyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-3)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.01 (s, 3H), 1.25 (s, 3H), 2.34 (s, 3H),3.30 (s, 3H), 3.69 (s, 3H), 5.13 (d, J = 13.4 Hz, 1H), 5.28 (d, J = 13.4Hz, 1H), 6.27 (s, 1H), 6.82 (d, J = 7.9 Hz, 1H), 6.84 (d, J = 7.9 Hz,1H), 7.04 (dd, J = 8.9, 4.6 Hz, 1H), 7.09 (dd, J = 9.0, 3.2 Hz, 1H),7.15 (td, J = 8.9, 3.2 Hz, 1H), 7.24 (d, J = 8.2 Hz, 2H), 7.60 (d, J =8.2 Hz, 2H) 7-(5-Fluoro-2-methoxyphenyl)-8-(3-methylbenzoyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-4)  

¹H-NMR (400 MHz, CDCl₃) δ 1.23 (s, 3H), 1.43 (s, 3H), 2.34 (s, 3H), 3.46(s, 3H), 3.73 (s, 3H), 3.82 (s, 1H), 5.18 (d, J = 13.4 Hz, 1H), 5.35 (d,J = 13.4 Hz, 1H), 6.77 (d, J = 8.1 Hz, 1H), 6.83 (dd, J = 8.7, 4.5 Hz,1H), 6.88 (d, J = 8.1 Hz, 1H), 6.96-7.02 (m, 2H), 7.23-7.32 (m, 2H),7.62-7.64 (m, 2H)7-(5-Fluoro-2-methoxyphenyl)-8-(2-methylbenzoyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-5)  

¹H-NMR (400 MHz, CDCl₃) δ 1.26 (s, 3H), 1.42 (s, 3H), 2.48 (s, 3H), 3.46(s, 3H), 3.71 (s, 3H), 3.82 (s, 1H), 5.13 (d, J = 13.3 Hz, 1H), 5.34 (d,J = 13.3 Hz, 1H), 6.77 (d, J = 8.0 Hz, 1H), 6.83-6.88 (m, 1H), 6.87 (d,J = 8.0 Hz, 1H), 6.98-7.01 (m, 1H), 6.99 (d, J = 8.1 Hz, 1H), 7.13-7.19(m, 2H), 7.35 (td, J = 8.6, 1.5 Hz, 1H), 7.66 (dd, J = 8.0, 1.2 Hz, 1H)7-(5-Fluoro-2-methoxyphenyl)-8-(thiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-6)  

¹H-NMR (400 MHz, CDCl₃) δ 1.20 (s, 3H), 1.42 (s, 3H), 3.46 (s, 3H), 3.74(s, 3H), 3.82 (s, 1H), 5.17 (d, J = 13.3 Hz, 1H), 5.33 (d, J = 13.3 Hz,1H), 6.77 (d, J = 8.0 Hz, 1H), 6.85 (dd, J = 8.6, 4.4 Hz, 1H), 6.87 (d,J = 8.0 Hz, 1H), 6.98-7.05 (m, 3H), 7.50 (dd, J = 4.9, 1.2 Hz, 1H), 7.63(dd, J = 3.6, 1.2 Hz, 1H)7-(5-Fluoro-2-methoxyphenyl)-8-(4-methoxybenzoyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-7)  

¹H-NMR (500 MHz, DMSO-d₆) δ 1.02 (s, 3H), 1.25 (s, 3H), 3.32 (s, 3H),3.69 (s, 3H), 3.80 (s, 3H), 5.11 (d, J = 13.3 Hz, 1H), 5.26 (d, J = 13.3Hz, 1H), 6.26 (s, 1H), 6.81 (d, J = 8.2 Hz, 1H), 6.84 (d, J = 8.2 Hz,1H), 6.95 (d, J = 8.7 Hz, 2H), 7.04 (dd, J = 8.8, 4.7 Hz, 1H), 7.09 (dd,J = 9.2, 3.1 Hz, 1H), 7.15 (td, J = 8.8, 3.1 Hz, 1H), 7.66 (d, J = 8.7Hz, 2H) 7-(4-Fluoro-2-methoxyphenyl)-8-phenoxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-8)   

¹H-NMR (400 MHz, DMSO-d₆) δ 0.87 (s, 3H), 1.09 (s, 3H), 3.32 (s, 3H),3.79 (s, 3H), 4.71 (d, J = 13.1 Hz, 1H), 5.10 (d, J = 13.1 Hz, 1H), 6.11(s, 1H), 6.53-6.56 (m, 2H), 6.76 (d, J = 8.1 Hz, 1H), 6.78-6.83 (m, 2H),6.81 (td, J = 8.3, 2.4 Hz, 1H), 6.98 (dd, J = 11.5, 2.4 Hz, 1H), 7.11(dd, J = 8.5, 7.3 Hz, 2H), 7.28 (dd, J = 8.4, 7.0 Hz, 1H)7-(5-Fluoro-2-methoxyphenyl)-8-phenoxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-9)  

¹H-NMR (400 MHz, CDCl₃) δ 1.00 (s, 3H), 1.31 (s, 3H), 3.49 (s, 3H), 3.72(br s, 1H), 3.77 (s, 3H), 4.80 (d, J = 12.9 Hz, 1H), 5.15 (d, J = 12.9Hz, 1H), 6.57-6.59 (m, 2H), 6.71 (d, J = 7.9 Hz, 1H), 6.79-6.83 (m, 1H),6.86 (dd, J = 8.9, 4.5 Hz, 1H), 6.86 (d, J = 7.9 Hz, 1H), 6.99-7.13 (m,4H) 7-(5-Fluoro-2-methoxyphenyl)-8-(3-fluorophenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-10)  

¹H-NMR (400 MHz, DMSO-d₆) δ 0.95 (s, 3H), 1.06 (s, 3H), 3.30 (s, 3H),3.74 (s, 3H), 4.79 (d, J = 12.6 Hz, 1H), 5.13 (d, J = 12.6 Hz, 1H), 6.19(s, 1H), 6.37-6.43 (m, 2H), 6.63 (td, J = 8.4, 2.0 Hz, 1H), 6.80 (d, J =8.1 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 7.05-7.18 (m, 4H)7-(5-Fluoro-2-methoxyphenyl)-8-(4-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-11)  

¹H-NMR (500 MHz, DMSO-d₆) δ 0.94 (s, 3H), 1.10 (s, 3H), 2.13 (s, 3H),3.32 (s, 3H), 3.74 (s, 3H), 4.69 (d, J = 13.1 Hz, 1H), 5.07 (d, J = 13.1Hz, 1H), 6.15 (s, 1H), 6.46 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.4 Hz,1H), 6.80 (d, J = 8.4 Hz, 1H), 6.92 (d, J = 8.4 Hz, 2H), 7.06 (dd, J =8.8, 4.7 Hz, 1H), 7.10 (dd, J = 9.0, 3.2 Hz, 1H), 7.15 (td, J = 8.8, 3.2Hz, 1H) 7-(5-Fluoro-2-methoxyphenyl)-8-(3-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-12)  

¹H-NMR (400 MHz, DMSO-d₆) δ 0.92 (s, 3H), 1.11 (s, 3H), 2.14 (s, 3H),3.33 (s, 3H), 3.75 (s, 3H), 4.72 (d, J = 12.7 Hz, 1H), 5.11 (d, J = 12.7Hz, 1H), 6.15 (s, 1H), 6.32-6.39 (m, 2H), 6.62 (d, J = 7.3 Hz, 1H), 6.79(d, J = 8.1 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H), 6.99 (t, J = 7.8 Hz, 1H),7.05-7.18 (m, 3H)7-(5-Fluoro-2-methoxyphenyl)-8-(2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-13)  

¹H-NMR (400 MHz, DMSO-d₆) δ 0.85 (s, 3H), 1.11 (s, 3H), 1.96 (s, 3H),3.29 (s, 3H), 3.78 (s, 3H), 4.80 (d, J = 13.3 Hz, 1H), 5.17 (d, J = 13.3Hz, 1H), 6.17 (s, 1H), 6.38 (d, J = 7.8 Hz, 1H), 6.69 (t, J = 7.1 Hz,1H), 6.79 (d, J = 8.1 Hz, 1H), 6.83 (d, J = 8.1 Hz, 1H), 6.94 (t, J =7.8 Hz, 1H), 7.00 (d, J = 7.1 Hz, 1H), 7.10 (dd, J = 9.0, 4.6 Hz, 1H),7.13-7.23 (m, 2H) 7-(5-Fluoro-2-methoxyphenyl)-8-phenylaminomethyl-l,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-14)  

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.44 (s, 3H), 3.50 (s, 3H), 3.76(br s, 1H), 3.80 (s, 3H), 4.02 (d, J = 12.0 Hz, 1H), 4.03 (br s, 1H),4.16 (d, J = 12.0 Hz, 1H), 6.34 (d, J = 7.6 Hz, 2H), 6.62 (t, J = 7.3Hz, 1H), 6.69 (d, J = 7.9 Hz, 1H), 6.79 (d, J = 7.9 Hz, 1H), 6.86 (dd, J= 9.0, 4.4 Hz, 1H), 6.90 (dd, J = 8.5, 3.2 Hz, 1H), 6.96-7.01 (m, 1H),7.03-7.07 (m, 2H)7-(5-Fluoro-2-methoxyphenyl)-8-(4-methylphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-15)  

¹H-NHR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.44 (s, 3H), 2.17 (s, 3H), 3.51(s, 3H), 3.75 (s, 1H), 3.80 (s, 3H), 3.90 (br s, 1H), 3.98 (d, J = 12.5Hz, 1H), 4.13 (d, J = 12.5 Hz, 1H), 6.27 (d, J = 8.3 Hz, 2H), 6.69 (d, J= 7.8 Hz, 1H), 6.78 (d, J = 7.8 Hz, 1H), 6.83-6.92 (m, 4H), 6.95-7.02(m, 1H) 7-(5-Fluoro-2-methoxyphenyl)-8-(3-methylphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-16)  

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.45 (s, 3H), 2.19 (s, 3H), 3.51(s, 3H), 3.75 (s, 1H), 3.80 (s, 3H), 3.95-4.04 (m, 2H), 4.10-4.19 (m,1H), 6.16 (d, J = 7.3 Hz, 1H), 6.17 (s, 1H), 6.44 (d, J = 7.3 Hz, 1H),6.69 (d, J = 8.1 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 6.84-7.01 (m, 4H)7-(5-Fluoro-2-methoxyphenyl)-8-(2-methylphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-17)  

¹H-NMR (400 MHz, CDCl₃) δ 1.21 (s, 3H), 1.43 (s, 3H), 1.92 (s, 3H), 3.45(s, 3H), 3.73 (s, 1H), 3.75 (s, 3H), 3.78 (s, 1H), 4.18-4.19 (m, 2H),6.36 (d, J = 7.8 Hz, 1H), 6.58 (t, J = 7.1 Hz, 1H), 6.71 (d, J = 7.9 Hz,1H), 6.82 (d, J = 7.9 Hz, 1H), 6.86 (dd, J = 8.9, 4.5 Hz, 1H), 6.92-7.03(m, 4H)1-Ethyl-7-(5-fluoro-2-methoxyphenyl)-8-(4-methylbenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-18)  

¹H-NMR (500 MHz, DMSO-d₆) δ 0.96 (s, 3H), 1.01 (t, J = 7.0 Hz, 3H), 1.27(s, 3H), 2.33 (s, 3H), 3.62 (dq, J = 7.0 Hz, 1H), 3.69 (s, 3H), 4.29(dq, J = 7.0 Hz, 1H), 5.10 (d, J = 13.4 Hz, 1H), 5.17 (d, J = 13.4 Hz,1H), 6.23 (s, 1H), 6.82 (d, J = 7.9 Hz, 1H), 6.85 (d, J = 7.9 Hz, 1H),7.05 (dd, J = 8.9, 4.6 Hz, 1H), 7.10 (dd, J = 9.0, 3.2 Hz, 1H), 7.16(td, J = 8.9, 3.2 Hz, 1H), 7.24 (d, J = 8.2 Hz, 2H), 7.59 (d, J = 8.2Hz, 2H) 1-(Propen-3-yl)-7-(5-fluoro-2-methoxyphenyl)-8-(4-methylbenzoyloxymethyl)-3,3-dimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 5-19)  

¹H-NMR (400 MHz, DMSO-d₆) δ 1.03 (s, 3H), 1.27 (s, 3H), 2.34 (s, 3H),3.64 (s, 3H), 4.27 (dd, J = 16.7, 5.4 Hz, 1H), 4.73-4.80 (m, 1H), 5.04(dd, J = 10.6, 1.6 Hz, 1H), 5.08 (d, J = 13.7 Hz, 1H), 5.10 (dd, J =17.3, 1.6 Hz, 1H), 5.18 (d, J = 13.7 Hz, 1H), 5.70 (ddt, J = 17.3, 10.6,5.4 Hz, 1H), 6.31 (s, 1H), 6.81 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 8.1Hz, 1H), 7.02 (dd, J = 9.0, 4.6 Hz, 1H), 7.04 (dd, J = 9.2, 3.2 Hz, 1H),7.13 (td, J = 9.0, 3.2 Hz, 1H), 7.25 (d, J = 8.0 Hz, 2H), 7.60 (d, J =8.0 Hz, 2H) 7-(2-Methoxy-4-methoxymethoxyphenyl)-8-(5-methylthiophen-2-ylcarbonyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H- quinoxalin-2-one(Compound No. 5-20)  

¹H-NMR (400 MHz, CDCl₃) δ 1.20 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.44(s, 3H), 3.51 (s, 3H), 3.75 (s, 4H), 5.13 (d, J = 13.4 Hz, 1H), 5.18 (d,J = 6.8 Hz, 1H), 5.21 (d, J = 6.8 Hz, 1H), 5.29 (d, J = 13.4 Hz, 1H),6.63 (d, J = 2.4 Hz, 1H), 6.66 (dd, J = 8.3, 2.4 Hz, 1H), 6.69 (d, J =3.6 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 8.1 Hz, 1H), 7.17(d, J = 8.3 Hz, 1H), 7.43 (d, J = 3.6 Hz, 1H)7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(4-methoxybenzoyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-21)  

¹H-NMR (500 MHz, CDCl₃) δ 1.20 (s, 3H), 1.43 (s, 3H), 2.70 (s, 3H), 3.48(s, 3H), 3.77 (s, 3H), 3.80 (s, 1H), 3.83 (s, 3H), 5.20 (d, J = 13.4 Hz,1H), 5.35 (d, J = 13.4 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H), 6.80 (d, J =2.1 Hz, 1H), 6.84 (dd, J = 8.2, 2.1 Hz, 1H), 6.84 (d, J = 8.7 Hz, 2H),6.91 (d, J = 7.9 Hz, 1H), 7.32 (d, J = 8.2 Hz, 1H), 7.32-7.36 (m, 2H),7.50 (t, J = 7.3 Hz, 1H), 7.80 (d, J = 8.7 Hz, 2H), 8.17 (d, J = 7.9 Hz,1H) 7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(2-methoxy-5-nitrophenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2- one(Compound No. 5-22)  

¹H-NMR (400 MHz, CDCl₃) δ 0.72 (s, 3H), 1.34 (s, 3H), 2.70 (s, 3H), 3.54(s, 3H), 3.69 (s, 1H), 3.85 (s, 3H), 3.86 (s, 3H), 5.02 (d, J = 13.8 Hz,1H), 5.47 (d, J = 13.8 Hz, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.76 (d, J =8.8 Hz, 1H), 6.86 (d, J = 2.2 Hz, 1H), 6.92 (d, J = 7.9 Hz, 1H), 6.97(dd, J = 8.3, 2.2 Hz, 1H), 7.15 (d, J = 2.6 Hz, 1H), 7.34 (d, J = 7.6Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.48-7.52 (m, 1H), 7.53 (d, J = 8.3Hz, 1H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 8.19 (d, J = 7.6 Hz, 1H)7-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(4-methylbenzoyloxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-23)  

¹H-NMR (400 MHz, CDCl₃) δ 1.20 (s, 3H), 1.43 (s, 3H), 2.36 (s, 3H), 2.69(s, 3H), 3.47 (s, 3H), 3.76 (s, 3H), 3.80 (s, 1H), 5.19 (d, J = 13.2 Hz,1H), 5.36 (d, J = 13.2 Hz, 1H), 6.77 (d, J = 8.1 Hz, 1H), 6.80 (d, J =2.2 Hz, 1H), 6.84 (dd, J = 8.2, 2.2 Hz, 1H), 6.91 (d, J = 8.1 Hz, 1H),7.16 (d, J = 8.1 Hz, 2H), 7.32 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 7.7 Hz,1H), 7.34 (t, J = 7.7 Hz, 1H), 7.48-7.52 (m, 1H), 7.74 (d, J = 8.1 Hz,2H), 8.17 (d, J = 7.7 Hz, 1H)8-(3-Fluorobenzoyloxymethyl)-7-[2-methoxy-4-(2-methylbenzoyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No.5-24)  

¹H-NMR (500 MHz, CDCl₃) δ 1.23 (s, 3H), 1.44 (s, 3H), 2.69 (s, 3H), 3.46(s, 3H), 3.77 (s, 3H), 3.82 (s, 1H), 5.23 (d, J = 13.3 Hz, 1H), 5.39 (d,J = 13.3 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 6.80 (d, J = 2.4 Hz, 1H),6.83 (dd, J = 8.2, 2.4 Hz, 1H), 6.92 (d, J = 8.2 Hz, 1H), 7.19-7.23 (m,1H), 7.29 (d, J = 8.2 Hz, 1H), 7.32-7.37 (m, 3H), 7.48-7.53 (m, 2H),7.64 (dt, J = 7.9, 1.2 Hz, 1H), 8.17 (d, J = 7.6 Hz, 1H)8-(5-Bromothiophen-2-ylcarbonyloxymethyl)-7-[2-methoxy-4-(2-methylbenzoyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 5-25)  

¹H-NMR (500 MHz, CDCl₃) δ 1.23 (s, 3H), 1.43 (s, 3H), 2.70 (s, 3H), 3.45(s, 3H), 3.78 (s, 3H), 3.81 (s, 1H), 5.17 (d, J = 13.3 Hz, 1H), 5.34 (d,J = 13.3 Hz, 1H), 6.78 (d, J = 7.9 Hz, 1H), 6.81 (d, J = 2.1 Hz, 1H),6.85 (dd, J = 7.9, 2.1 Hz, 1H), 6.91 (d, J = 7.9 Hz, 1H), 7.01 (d, J =4.0 Hz, 1H), 7.30 (d, J = 7.9 Hz, 1H), 7.33- 7.36 (m, 2H), 7.38 (d, J =4.0 Hz, 1H), 7.50 (td, J = 7.7, 1.4 Hz, 1H), 8.18 (d, J = 7.7 Hz, 1H)

Example 68-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-4-trifluoromethoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 6-1)

A mixture of7-bromo-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 8-1, 49.7 mg, 0.122 mmol),2-methoxy-4-trifluoromethoxyphenylboronic acid (58.1 mg, 0.246 mmol),cessium carbonate (119 mg, 0.36 mmol) andbis(triphenylphosphin)palladium(II)dichloride (12.0 mg, 0.0171 mmol) wassuspended in anhydrous N,N-dimethylformamide (0.5 ml) and stirred at 80°C. for 2 hours under argon atmosphere. After cooling down, ethyl acetate(100 mL) and water (100 mL) was added and partitioned. The organic layerwas washed with saturated brine (50 mL), dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled compound (52.7 mg) as acolorless amorphous product. (Yield 58%)

¹H-NMR (500 MHz, CDCl₃) δ 0.98 (s, 3H), 1.27 (s, 3H), 2.00 (s, 3H), 3.46(s, 3H), 3.74 (s, 1H), 3.83 (s, 3H), 4.81 (d, J = 13.4 Hz, 1H), 5.17 (d,J = 13.4 Hz, 1H), 6.05 (dd, J = 11.3, 2.4 Hz, 1H), 6.40 (td, J = 8.4,2.4 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H), 6.82 (d, J = 1.8 Hz, 1H), 6.86(d, J = 7.9 Hz, 1H), 6.89-6.92 (m, 2H), 7.31 (d, J = 8.2 Hz, 1H)Using any compounds among Reference Compounds No. 8-1˜8-4, 17,18-1˜18-5, 20-1, 20-2, and available compounds, the following Compounds(No. 6-2˜6-34 and 6-37˜6-43) were obtained by a method similar to thatof Compound No. 6-1. The following Compounds (No. 6-35 and 6-36) wereobtained by a method similar to that of Reference Compound No. 20-1using any compounds among Reference Compounds No. 19-2, 19-3, andavailable compounds followed by a method similar to that of Compound No.6-1 using Reference Compound No. 8-1 and available compounds.

¹H-NMR (400 MHz, CDCl₃) δ 1.00 (s, 3H), 1.33 (s, 3 H), 2.07 (s, 3H),3.44 (s, 3H), 3.72 (br s, 1H), 3.80 (s, 3H), 4.80 (d, J = 12.9 Hz, 1H),5.16 (d, J = 12.9 Hz, 1H), 6.33 (d, J = 8.1 Hz, 1H), 6.68-6.75 (m, 3H),6.72 (d, J = 8.1 Hz, 1H), 6.85 (d, J = 8.1 Hz, 1H), 6.93 (t, J = 7.9 Hz,1H), 7.01 (d, J = 7.9 Hz, 1H), 7.24-7.28 (m, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.06 (s, 3H), 1.32 (s, 3 H), 2.02 (s, 3H),3.45 (s, 3H), 3.80 (s, 1H), 4.87 (br s, 1H), 5.17 (br s, 1H), 6.10 (dd,J = 11.0, 2.4 Hz, 1H), 6.43 (td, J = 8.3, 2.4 Hz, 1H), 6.77 (d, J = 8.1Hz, 1H), 6.88-7.00 (m, 1H), 6.94 (d, J = 8.1 Hz, 1H), 7.12-7.19 (m, 1H),7.22 (td, J = 7.4, 1.2 Hz, 1H), 7.31- 7.45 (m, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 1.09 (s, 3H), 1.34 (s, 3 H), 2.03 (s, 3H),3.43 (s, 3H), 3.80 (s, 1H), 4.71 (d, J = 12.5 Hz, 1H), 5.18 (d, J = 12.5Hz, 1H), 6.14 (dd, J = 11.0, 2.4 Hz, 1H), 6.43 (td, J = 8.3, 2.4 Hz,1H), 6.77 (d, J = 8.0 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.91-6.95 (m,1H), 7.28-7.33 (m, 2H), 7.39-7.43 (m, 1 H), 7.45-7.49 (m, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.20 (s, 3H), 1.28 (s, 3 H), 2.04 (s, 3H),2.15 (s, 3H), 3.42 (s, 3H), 3.76 (s, 1H), 4.74 (d, J = 12.0 Hz, 1H),4.94 (d, J = 12.0 Hz, 1H), 6.14 (dd, J = 11.0, 2.4 Hz, 1H), 6.44 (td, J= 8.3, 2.4 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H),6.94 (t, J = 7.6 Hz, 1H), 7.16-7.29 (m, 4H)

¹H-NMR (500 MHz, CDCl₃) δ 1.06 (t, J = 7.6 Hz, 3H), 1.21 (s, 3H), 1.30(s, 3H), 2.04 (s, 3H), 2.42-2.55 (m, 2H), 3.40 (s, 3H), 3.76 (s, 1H),4.72 (d, J = 11.9 Hz, 1H), 4.90 (d, J = 11.9 Hz, 1H), 6.14 (dd, J =11.0, 2.4 Hz, 1H), 6.45 (td, J = 8.2, 2.4 Hz, 1H), 6.76 (d, J = 7.9 Hz,1H), 6.85 (d, J = 7.9 Hz, 1H), 6.95 (t, J = 7.3 Hz, 1H), 7.17-7.24 (m,2H), 7.28-7.32 (m, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 1.29 (s, 3H), 1.32 (s, 3 H), 2.06 (s, 3H),3.37 (s, 3H), 3.83 (s, 1H), 4.49 (d, J = 11.6 Hz, 1H), 4.88 (d, J = 11.6Hz, 1H), 6.21 (dd, J = 10.9, 2.5 Hz, 1H), 6.48 (td, J = 8.3, 2.5 Hz,1H), 6.76 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 8.1 Hz, 1H), 6.98 (t, J =7.5 Hz, 1H), 7.43-7.52 (m, 3H), 7.73 (d, J = 7.3 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.28 (s, 3 H), 2.01 (s, 3H),3.47 (s, 3H), 3.71 (s, 1H), 3.83 (s, 3H), 4.85 (d, J = 13.7 Hz, 1H),5.23 (d, J = 13.7 Hz, 1H), 6.05 (dd, J = 11.2, 2.4 Hz, 1H), 6.38 (td, J= 8.3, 2.4 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 6.88 (td, J = 7.6, 0.7 Hz,1H), 6.91 (d, J = 8.0 Hz, 1H), 6.99 (dd, J = 8.3, 0.7 Hz, 1H), 7.06 (td,J = 7.5, 1.1 Hz, 1H), 7.30-7.33 (m, 1H), 7.35- 7.40 (m, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.03 (s, 3H), 1.37 (s, 3 H), 2.02 (s, 3H),3.42 (s, 3H), 3.81 (s, 1H), 4.70 (d, J = 12.9 Hz, 1H), 5.18 (d, J = 12.9Hz, 1H), 6.09 (dd, J = 11.0, 2.4 Hz, 1H), 6.43 (td, J = 8.3, 2.4 Hz,1H), 6.77 (d, J = 8.1 Hz, 1H), 6.90 (d, J = 8.1 Hz, 1H), 6.93 (t, J =7.5 Hz, 1H), 7.34-7.52 (m, 4H)

¹H-NMR (400 MHz, CDCl₃) δ 1.09 (s, 3H), 1.33 (s, 3 H), 2.03 (s, 3H),2.38 (s, 3H), 3.43 (s, 3H), 3.78 (s, 1H), 4.68 (d, J = 12.5 Hz, 1H),5.20 (d, J = 12.5 Hz, 1H), 6.18 (dd, J = 11.2, 2.4 Hz, 1H), 6.43 (td, J= 8.3, 2.4 Hz, 1H), 6.77 (d, J = 8.1 Hz, 1H), 6.87 (d, J = 8.1 Hz, 1H),6.91-6.95 (m, 1H), 7.15-7.29 (m, 3H), 7.33-7.37 (m, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.25 (s, 3H), 1.28 (s, 3 H), 2.06 (s, 3H),3.42 (s, 3H), 3.62 (s, 3H), 3.76 (s, 1H), 4.69 (d, J = 12.0 Hz, 1H),4.97 (d, J = 12.0 Hz, 1H), 6.19 (dd, J = 10.9, 2.3 Hz, 1H), 6.46 (td, J= 8.3, 2.3 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H),6.96 (t, J = 7.7 Hz, 1H), 7.39-7.42 (m, 2H), 7.47-7.49 (m, 1H), 7.91(dd, J = 7.9, 1.5 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.96 (s, 3H), 1.27 (s, 3 H), 2.01 (s, 3H),3.46 (s, 3H), 3.72 (s, 1H), 3.81 (s, 3H), 4.81 (d, J = 13.4 Hz, 1H),5.17 (d, J = 13.4 Hz, 1H), 6.05 (dd, J = 11.0, 2.5 Hz, 1H), 6.40 (td, J= 8.3, 2.5 Hz, 1H), 6.71-6.73 (m, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.76(td, J = 7.9, 2.4 Hz, 1H), 6.86 (d, J = 7.9 Hz, 1H), 6.91 (t, J = 7.9Hz, 1H), 7.24-7.27 (m, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.01 (s, 3H), 1.29 (s, 3 H), 2.01 (s, 3H),3.44 (s, 3H), 3.75 (s, 1H), 3.79 (s, 3H), 4.82 (d, J = 13.3 Hz, 1H),5.18 (d, J = 13.3 Hz, 1H), 6.10 (dd, J = 11.2, 2.4 Hz, 1H), 6.41 (td, J= 8.3, 2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.88 (d, J = 8.1 Hz, 1H),6.88-6.94 (m, 2H), 7.02-7.08 (m, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3 H), 2.01 (s, 3H),3.45 (s, 3H), 3.73 (s, 1H), 3.82 (s, 3H), 4.80 (d, J = 13.4 Hz, 1H),5.17 (d, J = 13.4 Hz, 1H), 6.05 (dd, J = 11.3, 2.4 Hz, 1H), 6.40 (td, J= 8.0, 2.4 Hz, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.85 (d, J = 7.9 Hz, 1H),6.91 (t, J = 8.0 Hz, 1H), 6.97 (d, J = 1.8 Hz, 1H), 7.05 (dd, J = 8.1,1.8 Hz, 1H), 7.24 (d, J = 8.1 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.05 (s, 3H), 1.28 (s, 3 H), 2.02 (s, 3H),3.44 (s, 3H), 3.76 (s, 1H), 3.80 (s, 3H), 4.80 (d, J = 13.1 Hz, 1H),5.14 (d, J = 13.1 Hz, 1H), 6.11 (dd, J = 11.3, 2.4 Hz, 1H), 6.42 (td, J= 8.2, 2.4 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H), 6.87 (d, J = 7.9 Hz, 1H),6.90 (d, J = 8.6 Hz, 1H), 6.92 (d, J = 8.6 Hz, 1H), 7.29-7.30 (m, 1H),7.32 (d, J = 2.7 Hz, 1 H)

¹H-NMR (500 MHz, CDCl₃) δ 0.90 (s, 3H), 1.28 (s, 3 H), 2.01 (s, 3H),3.47 (s, 3H), 3.68 (s, 1H), 3.81 (s, 3H), 3.87 (s, 3H), 4.86 (d, J =13.6 Hz, 1H), 5.22 (d, J = 13.6 Hz, 1H), 6.04 (dd, J = 11.2, 2.4 Hz,1H), 6.38 (td, J = 8.4, 2.4 Hz, 1 H), 6.56 (d, J = 2.3 Hz, 1H), 6.60(dd, J = 8.2, 2.3 Hz, 1H), 6.70 (d, J = 7.9 Hz, 1H), 6.87-6.90 (m, 1H),6.88 (d, J = 7.9 Hz, 1H), 7.23 (d, J = 8.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.91 (s, 3H), 1.31 (s, 3 H), 2.01 (s, 3H),3.47 (s, 3H), 3.72 (s, 1H), 3.76 (s, 3H), 3.81 (s, 3H), 4.87 (d, J =13.7 Hz, 1H), 5.25 (d, J = 13.7 Hz, 1H), 6.09 (dd, J = 11.2, 2.4 Hz,1H), 6.39 (td, J = 8.3, 2.4 Hz, 1 H), 6.72 (d, J = 8.1 Hz, 1H),6.87-6.92 (m, 5H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.29 (s, 3 H), 2.01 (s, 3H),2.33 (s, 3H), 3.47 (s, 3H), 3.70 (br s, 1H), 3.79 (s, 3H), 4.84 (d, J =13.7 Hz, 1H), 5.22 (d, J = 13.7 Hz, 1H), 6.08 (dd, J = 11.2, 2.4 Hz,1H), 6.39 (td, J = 8.3, 2.4 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 6.87-6.91(m, 2H), 6.90 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 2.3 Hz, 1H), 7.16 (dd, J= 8.3, 2.3 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.09 (s, 3H), 1.28 (s, 3 H), 1.99 (s, 3H),3.45 (s, 3H), 3.78 (s, 1H), 3.88 (s, 3H), 4.77 (d, J = 12.8 Hz, 1H),5.11 (d, J = 12.8 Hz, 1H), 6.09 (dd, J = 11.0, 2.4 Hz, 1H), 6.42 (td, J= 8.4, 2.4 Hz, 1H), 6.76 (d, J = 7.9 Hz, 1H), 6.89 (d, J = 7.9 Hz, 1H),6.90-6.94 (m, 1H), 7.04 (d, J = 8.9 Hz, 1H), 7.56 (d, J = 2.1 Hz, 1H),7.62 (dd, J = 8.9, 2.1 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.88 (s, 3H), 1.26 (d, J = 6.9 Hz, 3H), 1.26(d, J = 6.9 Hz, 3H), 1.30 (s, 3H), 2.01 (s, 3H), 2.91 (septet, J = 6.9Hz, 1H), 3.49 (s, 3H), 3.70 (s, 1H), 3.81 (s, 3H), 4.86 (d, J = 13.8 Hz,1H), 5.25 (d, J = 13.8 Hz, 1H), 6.04 (dd, J = 11.2, 2.4 Hz, 1H), 6.37(td, J = 8.3, 2.4 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H), 6.86-6.90 (m, 1H),6.92 (d, J = 8.3 Hz, 1H), 6.92 (d, J = 8.1 Hz, 1H), 7.19 (d, J = 2.4 Hz,1H), 7.23 (dd, J = 8.3, 2.4 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.84 (s, 3H), 1.31 (s, 3 H), 1.34 (s, 9H),2.01 (s, 3H), 3.50 (s, 3H), 3.69 (s, 1H), 3.81 (s, 3H), 4.87 (d, J =13.9 Hz, 1H), 5.27 (d, J = 13.9 Hz, 1H), 6.01 (dd, J = 11.2, 2.4 Hz,1H), 6.36 (td, J = 8.3, 2.4 Hz, 1 H), 6.73 (d, J = 7.9 Hz, 1H),6.85-6.90 (m, 1H), 6.92 (d, J = 7.9 Hz, 1H), 6.92 (d, J = 8.5 Hz, 1H),7.36 (d, J = 2.4 Hz, 1H), 7.39 (dd, J = 8.5, 2.4 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.37 (s, 3 H), 2.00 (s, 3H),3.44 (s, 3H), 3.66 (d, J = 1.7 Hz, 3 H), 3.78 (br s, 1H), 4.80 (d, J =13.3 Hz, 1H), 5.28 (d, J = 13.3 Hz, 1H), 6.09 (dd, J = 11.1, 2.4 Hz,1H), 6.41 (td, J = 8.3, 2.4 Hz, 1H), 6.75 (d, J = 8.1 Hz, 1 H), 6.91 (t,J = 7.6 Hz, 1H), 6.91 (d, J = 8.1 Hz, 1H), 7.07-7.17 (m, 3H)

¹H-NMR (500 MHz, CDCl₃) δ 1.06 (s, 3H), 1.17 (s, 3 H), 2.02 (s, 3H),3.46 (s, 3H), 3.75 (br s, 1H), 3.82 (s, 3H), 5.02 (s, 2H), 6.15 (dd, J =11.3, 2.5 Hz, 1H), 6.39 (td, J = 8.3, 2.5 Hz, 1H), 6.73 (d, J = 8.1 Hz,1H), 6.78-6.83 (m, 2H), 6.88- 6.91 (m, 1H), 6.91 (d, J = 8.1 Hz, 1H),7.31 (td, J = 8.3, 6.6 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.03 (s, 3H), 1.37 (s, 3 H), 2.00 (s, 3H),3.42 (s, 3H), 3.59 (s, 3H), 3.83 (s, 1H), 4.76 (d, J = 13.2 Hz, 1H),5.24 (d, J = 13.2 Hz, 1H), 6.15 (dd, J = 11.0, 2.4 Hz, 1H), 6.44 (td, J= 8.3, 2.4 Hz, 1H), 6.76 (d, J = 7.8 Hz, 1H), 6.87-6.95 (m, 4H)

¹H-NMR (500 MHz, CDCl₃) δ 1.26 (s, 6H), 2.13 (s, 3 H), 3.45 (s, 3H),3.80 (br s, 1H), 4.86 (s, 2H), 6.22 (dd, J = 11.0, 2.4 Hz, 1H), 6.51(td, J = 8.2, 2.4 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 6.92 (d, J = 8.1Hz, 1 H), 7.01 (t, J = 7.5 Hz, 1H), 7.11-7.18 (m, 2H), 7.24- 7.29 (m,1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.08 (s, 3H), 1.27 (s, 3 H), 2.02 (s, 3H),3.43 (s, 3H), 3.77 (s, 1H), 3.80 (s, 3H), 4.76 (d, J = 13.0 Hz, 1H),5.10 (d, J = 13.0 Hz, 1H), 6.12 (dd, J = 11.0, 2.4 Hz, 1H), 6.44 (td, J= 7.9, 2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.79 (d, J = 10.7 Hz, 1H),6.84 (d, J = 8.1 Hz, 1H), 6.94 (t, J = 7.9 Hz, 1H), 7.33 (d, J = 8.2 Hz,1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.27 (s, 3 H), 2.01 (s, 3H),3.43 (s, 3H), 3.84 (s, 1H), 3.93 (s, 3H), 4.73 (d, J = 12.7 Hz, 1H),5.05 (d, J = 12.7 Hz, 1H), 6.12 (dd, J = 11.0, 2.4 Hz, 1H), 6.44 (td, J= 8.3, 2.4 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H),6.91-6.95 (m, 1H), 7.04 (d, J = 9.0 Hz, 1H), 8.21 (d, J = 2.8 Hz, 1H),8.27 (dd, J = 9.0, 2.8 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.05 (s, 3H), 1.31 (s, 3 H), 1.99 (s, 3H),3.45 (s, 3H), 3.85 (s, 1H), 3.93 (s, 3H), 4.75 (d, J = 13.2 Hz, 1H),5.15 (d, J = 13.2 Hz, 1H), 6.05 (dd, J = 11.0, 2.4 Hz, 1H), 6.43 (td, J= 8.3, 2.4 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 8.1 Hz, 1H),6.92 (t, J = 7.6 Hz, 1H), 7.47 (d, J = 8.2 Hz, 1H), 7.83 (d, J = 2.2 Hz,1H), 7.93 (dd, J = 8.2, 2.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.13 (s, 3H), 1.27 (s, 3 H), 2.02 (s, 3H),3.43 (s, 3H), 3.82 (s, 1H), 3.88 (s, 3H), 4.72 (d, J = 12.8 Hz, 1H),5.06 (d, J = 12.8 Hz, 1H), 6.10 (dd, J = 11.0, 2.4 Hz, 1H), 6.45 (td, J= 8.3, 2.4 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H),6.95 (t, J = 7.2 Hz, 1H), 7.02 (d, J = 8.5 Hz, 1H), 7.59 (d, J = 2.2 Hz,1H), 7.66 (dd, J = 8.5, 2.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.03 (s, 3H), 1.29 (s, 3 H), 2.00 (s, 3H),2.58 (s, 3H), 3.46 (s, 3H), 3.77 (s, 1H), 3.90 (s, 3H), 4.79 (d, J =13.2 Hz, 1H), 5.14 (d, J = 13.2 Hz, 1H), 6.07 (dd, J = 11.1, 2.5 Hz,1H), 6.41 (td, J = 8.3, 2.5 Hz, 1 H), 6.76 (d, J = 8.1 Hz, 1H),6.88-6.93 (m, 1H), 6.89 (d, J = 8.1 Hz, 1H), 7.03 (d, J = 8.8 Hz, 1H),7.92 (d, J = 2.3 Hz, 1H), 8.03 (dd, J = 8.8, 2.3 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.95 (s, 3H), 1.28 (s, 3 H), 2.03 (s, 3H),3.47 (s, 3H), 3.73 (br s, 1H), 3.84 (s, 3H), 4.89 (d, J = 13.7 Hz, 1H),5.23 (d, J = 13.7 Hz, 1H), 6.09 (dd, J = 11.0, 2.4 Hz, 1H), 6.40 (td, J= 8.3, 2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.89-6.96 (m, 4H), 7.37(d, J = 8.1 Hz, 1H), 7.52-7.56 (m, 2H), 7.64-7.69 (m, 1H), 8.22- 8.25(m, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 1.03 (s, 3H), 1.25 (s, 3 H), 2.01 (s, 3H),3.45 (s, 3H), 3.77 (s, 1H), 3.84 (s, 3H), 4.90 (d, J = 13.4 Hz, 1H),5.20 (d, J = 13.4 Hz, 1H), 6.17 (dd, J = 11.3, 2.4 Hz, 1H), 6.41 (td, J= 8.2, 2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.90 (t, J = 7.3 Hz, 1H),6.96 (d, J = 8.1 Hz, 1H), 7.02 (d, J = 8.8 Hz, 1H), 7.19 (d, J = 3.0 Hz,1H), 7.23 (dd, J = 8.8, 3.0 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.64 (t,J = 7.8 Hz, 1H), 8.19 (d, J = 7.8 Hz, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 0.93 (s, 3H), 1.29 (s, 3 H), 2.01 (s, 3H),3.45 (s, 3H), 3.73 (s, 1H), 3.75 (s, 3H), 4.87 (d, J = 13.7 Hz, 1H),5.01 (s, 1H), 5.23 (d, J = 13.7 Hz, 1H), 6.10 (dd, J = 11.0, 2.4 Hz,1H), 6.39 (td, J = 8.4, 2.4 Hz, 1 H), 6.71 (d, J = 7.9 Hz, 1H),6.83-6.86 (m, 3H), 6.89 (d, J = 7.9 Hz, 1H), 6.90 (t, J = 7.3 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.03 (s, 3H), 1.30 (s, 3 H), 1.99 (s, 3H),3.45 (s, 3H), 3.81 (s, 1H), 3.86 (s, 3H), 4.75 (d, J = 13.1 Hz, 1H),5.14 (d, J = 13.1 Hz, 1H), 6.04 (dd, J = 11.0, 2.4 Hz, 1H), 6.43 (td, J= 8.2, 2.4 Hz, 1H), 6.75 (d, J = 7.9 Hz, 1H), 6.84 (d, J = 7.9 Hz, 1H),6.91-6.94 (m, 1H), 7.20 (d, J = 1.5 Hz, 1H), 7.35 (dd, J = 7.6, 1.5 Hz,1H), 7.40 (d, J = 7.6 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.31 (s, 3 H), 2.00 (s, 3H),2.66 (s, 3H), 3.46 (s, 3H), 3.77 (s, 1H), 3.90 (s, 3H), 4.79 (d, J =13.5 Hz, 1H), 5.20 (d, J = 13.5 Hz, 1H), 6.03 (dd, J = 11.1, 2.4 Hz,1H), 6.40 (td, J = 8.2, 2.4 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 1H),6.89-6.92 (m, 1H), 6.89 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 7.8 Hz, 1H),7.60 (d, J = 1.6 Hz, 1H), 7.64 (dd, J = 7.8, 1.6 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.90 (s, 3H), 1.28 (s, 3 H), 2.01 (s, 3H),2.43 (s, 3H), 3.46 (s, 3H), 3.68 (s, 1H), 3.81 (s, 3H), 4.86 (d, J =13.7 Hz, 1H), 5.23 (d, J = 13.7 Hz, 1H), 6.05 (dd, J = 11.3, 2.4 Hz,1H), 6.38 (td, J = 8.2, 2.4 Hz, 1 H), 6.71 (d, J = 8.1 Hz, 1H), 6.80 (s,1H), 6.87-6.90 (m, 2H), 6.89 (d, J = 8.1 Hz, 1H), 7.20 (d, J = 7.6 Hz,1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.08 (s, 3H), 1.24 (s, 3 H), 2.01 (s, 3H),3.45(s, 3H), 3.81 (s, 1H), 3.88 (s, 3H), 3.89 (s, 3H), 4.80 (d, J = 13.1 Hz,1H), 5.11 (d, J = 13.1 Hz, 1H), 6.09 (dd, J = 11.1, 2.4 Hz, 1H), 6.41(td, J = 8.3, 2.4 Hz, 1 H), 6.75 (d, J = 7.8 Hz, 1H), 6.89-6.92 (m, 1H),6.90 (d, J = 7.8 Hz, 1H), 7.01 (d, J = 8.5 Hz, 1H), 7.99 (d, J = 2.2 Hz,1H), 8.07 (dd, J = 8.5, 2.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.22 (s, 3H), 1.43 (s, 3 H), 3.47 (s, 3H),3.71 (s, 3H), 3.78 (s, 1H), 3.84 (s, 3H), 4.09-4.11 (m, 2H), 4.39 (br s,1H), 6.30 (dd, J = 7.8, 1.5 Hz, 1H), 6.57 (td, J = 7.8, 1.5 Hz, 1H),6.65 (dd, J = 8.1, 1.5 Hz, 1H), 6.70-6.74 (m, 1H), 6.71 (d, J = 8.1 Hz,1H), 6.80 (d, J = 8.1 Hz, 1H), 6.96 (d, J = 8.7 Hz, 1H), 7.45 (d, J =2.0 Hz, 1H), 7.56 (dd, J = 8.7, 2.0 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.16 (s, 3H), 1.42 (s, 3 H), 3.46 (s, 3H),3.50 (s, 3H), 3.70 (s, 1H), 3.73 (s, 3H), 3.77 (s, 3H), 4.13 (d, J = 5.3Hz, 2H), 4.52 (t, J = 5.3 Hz, 1H), 5.19 (s, 2H), 6.34 (dd, J = 7.6, 1.5Hz, 1H), 6.56 (td, J = 7.6, 1.5 Hz, 1H), 6.61 (d, J = 2.4 Hz, 1H),6.65-6.67 (m, 2H), 6.68 (d, J = 7.9 Hz, 1H), 6.72 (td, J = 7.6, 1.5 Hz,1H), 6.80 (d, J = 7.9 Hz, 1H), 7.07 (d, J = 8.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.19 (s, 3H), 1.42 (s, 3 H), 2.29 (s, 3H),3.47 (s, 3H), 3.71 (s, 1H), 3.73 (s, 3H), 3.76 (s, 3H), 4.13 (br s, 2H),4.52 (br s, 1H), 6.34 (dd, J = 7.8, 1.4 Hz, 1H), 6.56 (td, J = 7.8, 1.4Hz, 1H), 6.66 (dd, J = 7.8, 1.4 Hz, 1H), 6.69 (d, J = 8.1 Hz, 1H), 6.72(td, J = 7.8, 1.4 Hz, 1H), 6.80 (d, J = 8.2 Hz, 1H), 6.82 (d, J = 8.1Hz, 1H), 6.99 (d, J = 2.0 Hz, 1H), 7.09 (dd, J = 8.2, 2.0 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.17 (s, 3H), 1.40 (s, 3 H), 1.85 (s, 3H),3.42 (s, 3H), 3.51 (s, 3H), 3.73 (s, 1H), 3.77 (s, 3H), 3.83 (br s, 1H),4.13-4.23 (m, 2H), 5.20 (s, 2H), 6.03 (dd, J = 11.7, 2.5 Hz, 1H), 6.22(td, J = 8.4, 2.5 Hz, 1H), 6.65 (d, J = 2.3 Hz, 1H), 6.70 (d, J = 7.8Hz, 1H), 6.71 (dd, J = 8.3, 2.3 Hz, 1H), 6.81-6.85 (m, 1H), 6.83 (d, J =7.8 Hz, 1H), 7.11 (d, J = 8.3 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.20 (s, 3H, 1.43 (s, 3 H), 3.47 (s, 3H), 3.70(s, 3H), 3.76 (s, 1H), 3.85 (s, 3H), 3.88 (s, 3H), 4.09 (d, J = 5.3 Hz,2H), 4.41 (t, J = 5,3 Hz, 1H), 6.31 (dd, J = 7.7, 1.4 Hz, 1H), 6.56 (td,J = 7.7, 1.4 Hz, 1H), 6.64 (dd, J = 7.7, 1.5 Hz, 1H), 6.71 (d, J = 8.0Hz, 1H), 6.71 (td, J = 7.7, 1.5 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 6.93(d, J = 8.5 Hz, 1H), 7.88 (d, J = 2.2 Hz, 1H), 8.01 (dd, J = 8.5, 2.2Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.25 (s, 3H), 1.43 (s, 3 H), 3.47 (s, 3H),3.70 (s, 3H), 3.82 (s, 1H), 3.89 (s, 3H), 4.06 (d, J = 14.1 Hz, 1H),4.13 (d, J = 14.1 Hz, 1H), 4.30 (br s, 1H), 6.28 (dd, J = 7.8, 1.4 Hz,1H), 6.57 (td, J = 7.8, 1.4 Hz, 1H), 6.64 (dd, J = 7.8, 1.4 Hz, 1H),6.70 (td, J = 7.8, 1.4 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H), 6.79 (d, J =7.9 Hz, 1H), 6.94 (d, J = 9.2 Hz, 1H), 8.09 (d, J = 2.7 Hz, 1H), 8.20(dd, J = 9.2, 2.7 Hz, 1H)

Example 78-(5-Fluoro-2-methylphenoxymethyl)-7-(2-nitrophenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 7-1)

A mixture of7-(5,5-dimethyl[1,3,2]dioxaborinan-2-yl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 21, 68.2 mg, 0.155 mmol), 2-nitro-1-iodobenzene(79.0 mg, 0.317 mmol), sodium hydrogen carbonate (41.5 mg, 0.494 mmol)and tetrakis(triphenylphosphine)palladium (0) (19.0 mg, 0.0164 mmol) wassuspended in mixed solvent of anhydrous N,N-dimethylformamide (0.5 ml)and water (0.5 mL), and stirred at 120° C. for 30 minutes by irradiatedmicrowave. After cooling down, ethyl acetate (15 mL) and water (15 mL)were added and partitioned. The organic layer was washed with saturatedbrine (15 mL), dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. The obtained residue waspurified by silica gel column chromatography (hexane-ethyl acetate) togive the titled compound (42.6 mg) as a yellow solid. (Yield 61%)

¹H-NMR (400 MHz, CDCl₃) δ 1.30 (s, 6H), 2.09 (s, 3H), 3.42 (s, 3H), 3.84(s, 1H), 4.62 (d, J = 11.5 Hz, 1H), 4.93 (d, J = 11.5 Hz, 1H), 6.24 (dd,J = 10.7, 2.4 Hz, 1H), 6.49 (td, J = 8.3, 2.4 Hz, 1H), 6.75 (d, J = 8.0Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.99 (t, J = 7.4 Hz, 1H), 7.46-7.57(m, 3H), 7.92 (dd, J = 8.1, 0.7 Hz, 1H)Using any compounds among Reference Compounds No. 22 and availablecompounds, the following Compound (No. 7-2) was obtained by a methodsimilar to that of Compound No. 7-1.

¹H-NMR (400 MHz, CDCl₃) δ 1.15 (s, 3H), 1.36 (s, 3 H, 2.04 (s, 3H), 3.45(s, 3H), 3.88 (s, 1H), 4.72 (d, J = 12.4 Hz, 1H), 5.21 (d, J = 12.4 Hz,1H), 6.13 (dd, J = 11.0, 2.4 Hz, 1H), 6.46 (td, J = 8.3, 2.4 Hz, 1H),6.80 (d, J = 8.1 Hz, 1H), 6.94 (d, J = 8.1 Hz, 1H), 6.96 (t, J = 7.6 Hz,1H), 7.45 (td, J = 7.7, 1.4 Hz, 1H), 7.54 (dd, J = 7.7, 0.9 Hz, 1H),7.61 (td, J = 7.7, 1.4 Hz, 1H), 7.75 (dd, J = 7.7, 0.9 Hz, 1H)

Example 87-(5-Amino-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 8-1)

A mixture of8-(5-fluoro-2-methylphenoxymethyl)-7-(2-methoxy-5-nitrophenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 6-27, 18.8 mg, 0.0392 mmol) and tin chloride (II) (23.0mg, 0.121 mmol) was suspended in mixed solvent of anhydrousN,N-dimethylformamide (0.25 ml) and anhydrous ethanol (0.5 mL), andstirred at 80° C. overnight. After cooling down, the reaction mixturewas diluted with ethyl acetate (10 mL) and saturated aqueous sodiumhydrogen carbonate solution was added thereto until the pH became 9.After the precipitate was filtered, the filtrate was washed with water(50 mL) and saturated brine (50 mL) successively, dried over anhydrousmagnesium sulfate, and then the solvent was removed under reducedpressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled compound (8.2mg) as a brown solid. (Yield 47%)

¹H-NMR (400 MHz, CDCl₃) δ 0.89 (s, 3H), 1.31 (s, 3H), 2.01 (s, 3H), 3.46(s, 3H), 3.72 (s, 3H), 3.81 (s, 1H), 4.88 (d, J = 13.7 Hz, 1H), 5.26 (d,J = 13.7 Hz, 1H), 6.11 (dd, J = 11.4, 2.5 Hz, 1H), 6.39 (td, J = 8.3,2.5 Hz, 1H), 6.70- 6.73 (m, 3H), 6.82 (d, J = 8.8 Hz, 1H), 6.89 (t, J =7.2 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H)Using Compound No. 6-28, the following Compound (No. 8-2) was obtainedby a method similar to that of Compound No. 8-1.

¹H-NMR (400 MHz, CDCl₃) δ 0.87 (s, 3H), 1.28 (s, 3H), 2.01 (s, 3H), 3.47(s, 3H), 3.64 (s, 1H), 3.78 (s, 3H), 4.89 (d, J = 13.7 Hz, 1H), 5.23 (d,J = 13.7 Hz, 1H), 6.05 (dd, J = 11.2, 2.4 Hz, 1H), 6.33 (d, J = 2.2 Hz,1 H), 6.37 (td, J = 8.4, 2.4 Hz, 1H), 6.40 (dd, J = 8.0, 2.2 Hz, 1H),6.68 (d, J = 8.1 Hz, 1H), 6.88 (d, J = 8.1 Hz, 1H), 6.88 (t, J = 7.6 Hz,1H), 7.10 (d, J = 8.0 Hz, 1 H)

Example No. 98-(5-Fluoro-2-methylphenoxymethyl)-7-(5-hydroxymethyl-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 9-1)

8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-5-methoxycarbonylphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 6-37, 50.2 mg, 0.102 mmol) was dissolved in anhydroustetrahydrofuran (0.5 ml), and lithium aluminum hydride (6.8 mg, 0.18mmol) was added thereto at 0° C. After the reaction mixture was stirredat same temperature for 30 minutes, ethyl acetate (1 mL) and water (1mL) were added thereto successively. Moreover ethyl acetate (10 mL) andwater (10 mL) were added and partitioned. The organic layer was washedwith saturated brine (10 mL), dried over anhydrous magnesium sulfate,and then the solvent was removed under reduced pressure. The obtainedresidue was purified by silica gel column chromatography (hexane-ethylacetate) to give the titled compound (29.8 mg) as a pale yellow solid.(Yield 47%)

¹H-NMR (500 MHz, CDCl₃) δ 0.97 (s, 3H), 1.29 (s, 3H), 2.01 (s, 3H), 3.47(s, 3H), 3.80 (br s, 1H), 3.83 (s, 3H), 4.66 (s, 2H), 4.81 (d, J = 13.3Hz, 1H), 5.20 (d, J = 13.3 Hz, 1H), 6.07 (dd, J = 11.3, 2.4 Hz, 1H),6.39 (td, J = 8.4, 2.4 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H), 6.89-6.91 (m,1H), 6.91 (d, J = 7.9 Hz, 1H), 6.97 (d, J = 8.5 Hz, 1H), 7.32 (d, J =2.2 Hz, 1H), 7.37 (dd, J = 8.5, 2.2 Hz, 1H)Using Compound No. 6-42, the following Compound (No. 9-2) was obtainedby a method similar to that of Compound No. 9-1.

¹H-NMR (400 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 3.47 (s, 3H), 3.73(s, 4H), 3.79 (s, 3H), 4.07 (d, J = 13.7 Hz, 1H), 4.13 (d, J = 13.7 Hz,1H), 4.47 (br s, 1 H), 4.61 (d, J = 5.9 Hz, 2H), 6.32 (dd, J = 7.8, 1.5Hz, 1H), 6.56 (td, J = 7.8, 1.5 Hz, 1H), 6.67 (dd, J = 7.8, 1.4 Hz, 1H),6.70 (d, J = 7.8 Hz, 1H), 6.73 (td, J = 7.8, 1.4 Hz, 1H), 6.82 (d, J =7.8 Hz, 1H), 6.89 (d, J = 8.3 Hz, 1H), 7.19 (d, J = 2.2 Hz, 1H), 7.29(dd, J = 8.3, 2.2 Hz, 1H)

Example 107-(5-Carboxy-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 10-1)

8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-5-methoxycarbonylphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 6-37, 50.5 mg, 0.103 mmol) was dissolved in mixed solventof tetrahydrofuran (1 mL) and methanol (1 mL), and 4N aqueous sodiumhydroxide solution (0.5 mL) was added thereto and stirred at roomtemperature overnight. Ethyl acetate (15 mL) and 0.25N aqueous HClsolution (20 mL) were added to the reaction mixture and partitioned. Theorganic layer was washed with saturated brine (15 mL), dried overanhydrous magnesium sulfate, and then the solvent was removed underreduced pressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate). The obtained materials werefiltered with chloroform (3 mL) to give the titled compound (20.3 mg) asa pale yellow solid. (Yield 42%)

¹H-NMR (400 MHz, DMSO-d₆) δ 0.83 (s, 3H), 1.11 (s, 3H), 1.92 (s, 3H),3.32 (s, 3H), 3.86 (s, 3H), 4.75 (d, J = 13.7 Hz, 1H), 5.20 (d, J = 13.7Hz, 1H), 6.15-6.17 (m, 2H), 6.49 (t, J = 7.7 Hz, 1H), 6.83 (s, 2 H),6.99 (t, J = 7.7 Hz, 1 H), 7.19 (d, J = 8.4 Hz, 1 H), 7.82 (s, 1H), 7.96(d, J = 8.4 Hz, 1H), 12.6 (br s, 1H)Using Compound No. 6-42, the following Compound (No. 10-2) was obtainedby a method similar to that of Compound No. 10-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 0.99 (s, 3H), 1.23 (s, 3 H), 3.31 (s, 3H),3.64 (s, 3H), 3.83 (s, 3H), 4.05 (d, J = 4.9 Hz, 2H), 4.44 (t, J = 4.9Hz, 1H), 6.15 (s, 1H), 6.23 (d, J = 7.8 Hz, 1H), 6.46 (t, J = 7.8 Hz,1H),6.57 (t, J = 7.8 Hz, 1H), 6.67 (d, J = 7.8 Hz, 1H), 6.73 (d, J = 8.0Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 7.16 (d, J = 8.7 Hz, 1H), 7.69 (d, J= 2.2 Hz, 1H), 7.93 (dd, J = 8.7, 2.2 Hz, 1H), 12.60 (br s, 1H)

Example 118-(5-Fluoro-2-methylphenoxymethyl)-7-(4-hydroxy-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 11)

7-(4-Benzoyloxy-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 6-31, 422 mg, 0.761 mmol) was dissolved in mixed solventof methanol (2 mL) and tetrahydrofuran (2 mL), and 4N aqueous sodiumhydroxide solution (0.761 mL, 3.04 mmoL) was added thereto. After thereaction mixture was stirred at room temperature for 40 minutes, water(100 mL) and 1N aqueous HCl solution (4 mL) were added thereto. Afterthe mixture was extracted with ethyl acetate (100 mL), the organic layerwas washed with water (100 mL) and saturated brine (50 mL) successively,dried over anhydrous magnesium sulfate, and then the solvent was removedunder reduced pressure. The obtained residue was filtered with a mixedsolvent of hexane (10 mL) and ethyl acetate (10 mL) to give the titledcompound (292 mg) as a colorless solid. (Yield 85%)

¹H-NMR (400 MHz, CDCl₃) δ 0.91 (s, 3H), 1.28 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.68 (br s, 1H), 3.80 (s, 3H), 4.85 (d, J = 13.4 Hz, 1H), 4.92(s, 1H), 5.21 (d, J = 13.4 Hz, 1H), 6.05 (dd, J = 11.4, 2.5 Hz, 1H),6.38 (td, J = 8.4, 2.5 Hz, 1H), 6.50-6.53 (m, 2H), 6.70 (d, J = 8.1 Hz,1H), 6.87 (d, J = 8.1 Hz, 1H), 6.87- 6.91 (m, 1H), 7.16 (d, J = 8.3 Hz,1H)

Example 127-(2-Methoxy-4-methoxymethoxyphenyl)-8-[N-(2-(9-fluorenylmethoxycarbonyl)aminomethyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 12-1)

7-(2-Methoxy-4-methoxymethoxyphenyl)-8-(2-methoxyphenylaminomethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 6-39, 104 mg, 0.212 mmol) and sodium hydrogen carbonate(22.0 mg, 0.262 mmol) were dissolved in mixed solvent of 1,4-dioxane(1.5 mL) and water (1 mL), and 9-fluorenylmethoxycarbonyl chloride (60.3mg, 0.233 mmol) was added thereto. After the reaction mixture wasstirred at room temperature for 30 minutes, the mixture was diluted withethyl acetate (50 mL). The mixture was washed with water (50 mL) andsaturated brine (50 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled compound (149 mg) as acolorless amorphous product. (Yield 99%)

¹H-NMR (400 MHz, CDCl₃) δ 1.28 (s, 3H), 1.38 (s, 3H), 3.34-3.89 (m,16H), 4.36-4.63 (m, 1H), 4.97- 5.02 (m, 1H), 5.17 (s, 1H), 5.46-5.65 (m,1H), 6.36- 7.33 (m, 15H), 7.64-7.67 (m, 2H)Using any compounds among Compounds No. 6-41 and available compounds,the following Compound (No. 12-2) was obtained by a method similar tothat of Compound No. 12-1.

¹H-NMR (400 MHz, CDCl₃) δ 1.26 (s, 3H), 1.41 (s, 3 H), 1.87 (s, 3H),3.36-4.27 (m, 13H), 4.66-5.21 (m, 4H), 6.07-7.64 (m, 16H)

Example 137-(4-Hydroxy-2-methoxyphenyl)-8-[N-(2-methoxyphenyl)-N-(9-fluorenylmethoxycarbonyl)aminomethyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 13-1)

7-(2-Methoxy-4-methoxymethoxyphenyl)-8-[N-(2-methoxyphenyl)-N-(9-fluorenylmethoxycarbonyl)aminomethyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 12-1, 137 mg, 0.192 mmol) was dissolved in 1,4-dioxane (1mL) and 4N hydrochloride/1,4-dioxane solution (144 μL, 0.576 mmol) wasadded thereto. After the reaction mixture was stirred at roomtemperature for 2 hours, the mixture was diluted with ethyl acetate (100mL). The mixture was washed with water (100 mL) and saturated brine (50mL) successively, dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. The obtained residue waspurified by silica gel column chromatography (hexane-ethyl acetate) togive the titled compound (71.6 mg) as a colorless solid. (Yield 56%)

¹H-NMR (400 MHz, CDCl₃) δ 1.27 (s, 3H), 1.38 (s, 3 H), 3.32 (s, 3H),3.49-4.15 (m, 10H), 4.39-4.59 (m, 1H), 5.23-5.90 (m, 2H), 6.29-7.33 (m,15H), 7.62-7.66 (m, 2H)Using Compounds No. 5-20 and 12-2, the following Compounds (No. 13-2 and13-3) were obtained by a method similar to that of Compound No. 13-1.

¹H-NMR (400 MHz, CDCl₃) δ 1.20 (s, 3H), 1.42 (s, 3 H), 2.47 (s, 3H),3.45 (s, 3H), 3.73 (s, 3H), 3.76 (s, 1H), 5.14 (d, J = 13.3 Hz, 1H),5.17 (s, 1H), 5.27 (d, J = 13.3 Hz, 1H), 6.42 (dd, J = 8.2, 2.3 Hz, 1H),6.46 (d, J = 2.3 Hz, 1H), 6.69 (d, J = 3.9 Hz, 1H), 6.74 (d, J = 8.0 Hz,1H), 6.86 (d, J = 8.0 Hz, 1H), 7.11 (d, J = 8.2 Hz, 1H), 7.45 (d, J =3.9 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.26 (s, 3H), 1.40 (s, 3 H), 1.89 (s, 3H),3.33- 4.54 (m, 10H), 5.15- 5.58 (m, 3H), 6.04- 7.64 (m, 16H)

Example 147-(4-Butyryloxy-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 14-1)

8-(5-Fluoro-2-methylphenoxymethyl)-7-(4-hydroxy-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 11, 25 mg, 0.055 mmol) was dissolved in tetrahydrofuran (1mL), and triethylamine (20 μL, 0.14 mmol) and butyryl chloride (7.6 μL,0.073 mmol) were added successively. After the reaction mixture wasstirred at room temperature for 1 hour, the mixture was purified bysilica gel column chromatography (hexane-ethyl acetate) to give thetitled compound (27 mg) as a colorless amorphous product. (Yield 92%)

¹H-NMR (500 MHz, CDCl₃) δ 0.93 (s, 3H), 1.07 (t, J = 7.3 Hz, 3H), 1.27(s, 3H), 1.78-1.86 (m, 2H), 2.01 (s, 3H), 2.58 (t, J = 7.3 Hz, 2H), 3.46(s, 3H), 3.71 (s, 1H), 3.81 (s, 3H), 4.85 (d, J = 13.6 Hz, 1H), 5.20 (d,J = 13.6 Hz, 1H), 6.06 (dd, J = 11.3, 2.4 Hz, 1H), 6.39 (td, J = 8.2,2.4 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.75 (d, J = 2.3 Hz, 1H), 6.81(dd, J = 8.2, 2.3 Hz, 1H), 6.88-6.91 (m, 1H), 6.88 (d, J = 8.1 Hz, 1H),7.30 (d, J = 8.2 Hz, 1H)Using any compounds among Compounds No. 8-2, 11, 13-2, and availablecompounds, the following Compounds (No. 14-2˜14-62) were obtained by amethod similar to that of Compound No. 14-1.

¹H-NMR (500 MHz, DMSO-d₆) δ 0.80 (s, 3H), 1.07 (s, 3H), 1.94 (s, 3H),2.62 (s, 3H), 3.34 (s, 3H), 3.82 (s, 3H), 4.88 (d, J = 13.9 Hz, 1H),5.25 (d, J = 13.9 Hz, 1H), 6.15 (dd, J = 11.6, 2.4 Hz, 1H), 6.15 (s,1H), 6.50 (td, J = 8.5, 2.4 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.86 (d,J = 8.1 Hz, 1H), 7.00 (dd, J = 8.1, 2.1 Hz, 1H), 7.00-7.02 (m, 1H), 7.13(d, J = 2.1 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 7.5 Hz, 1H),7.43 (d, J = 7.5 Hz, 1H), 7.59 (td, J = 7.5, 1.4 Hz, 1H), 8.11-8.13 (m,1H)

¹H-NMR (400 MHz, DMSO-d₆) δ 0.80 (s, 3H), 1.07 (s, 3H), 1.93 (s, 3H),3.33 (s, 3H), 3.82 (s, 3H), 3.89 (s, 3H), 4.87 (d, J = 13.8 Hz, 1H),5.24 (d, J = 13.8 Hz, 1H), 6.14 (dd, J = 11.2, 2.6 Hz, 1H), 6.15 (s,1H), 6.50 (td, J = 8.4, 2.6 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H), 6.85 (d,J = 8.1 Hz, 1H), 6.95 (dd, J = 8.2, 2.2 Hz, 1H), 6.98-7.02 (m, 1H), 7.05(d, J = 2.2 Hz, 1H), 7.12 (td, J = 7.4, 0.8 Hz, 1H), 7.25 (dd, J = 8.7,0.8 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.66 (ddd, J = 8.7, 7.4, 1.7 Hz,1H), 7.95 (dd, J = 7.4, 1.7 Hz, 1H)

¹H-NMR (500 MHz, DMSO-d₆) δ 0.80 (s, 3H), 1.08 (s, 3H), 1.93 (s, 3H),3.34 (s, 3H), 3.83 (s, 3H), 4.87 (d, J = 13.9 Hz, 1H), 5.24 (d, J = 13.9Hz, 1H), 6.16 (dd, J = 11.6, 2.4 Hz, 1H), 6.16 (s, 1H), 6.50 (td, J =8.2, 2.4 Hz, 1H), 6.82 (d, J = 7.9 Hz, 1H), 6.86 (d, J = 7.9 Hz, 1H),6.98- 7.03 (m, 2H), 7.14 (d, J = 2.1 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H),7.56-7.60 (m, 1H), 7.69- 7.70 (m, 2H), 8.13-8.15 (m, 1H)

¹H-NMR (400 MHz, DMSO-d₆) δ 0.81 (s, 3H), 1.08 (s, 3H), 1.93 (s, 3H),3.33 (s, 3H), 3.81 (s, 3H), 4.86 (d, J = 13.8 Hz, 1H), 5.24 (d, J = 13.8Hz, 1H), 6.15 (dd, J = 12.0, 2.5 Hz, 1H), 6.16 (s, 1H), 6.51 (td, J =8.4, 2.5 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 8.1 Hz, 1H),6.99-7.03 (m, 1H), 7.02 (dd, J = 8.0, 2.2 Hz, 1H), 7.17 (d, J = 2.2 Hz,1H), 7.35 (d, J = 8.0 Hz, 1H), 7.68 (t, J = 8.0 Hz, 1H), 7.86 (ddd, J =8.0, 2.2, 1.0 Hz, 1H), 8.10- 8.13 (m, 1H), 8.14-8.18 (m, 1H)

¹H-NMR (400 MHz, DMSO-d₆) δ 0.86 (s, 3H), 1.07 (s, 3H), 1.93 (s, 3H),3.33 (s, 3H), 3.81 (s, 3H), 4.87 (d, J = 13.7 Hz, 1H), 5.24 (d, J = 13.7Hz, 1H), 6.15 (dd, J = 11.1, 2.6 Hz, 1H), 6.16 (s, 1H), 6.51 (td, J =8.3, 2.6 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 8.1 Hz, 1H),6.99- 7.02 (m, 1H), 7.01 (dd, J = 8.2, 2.2 Hz, 1H), 7.14 (d, J = 2.2 Hz,1H), 7.34 (d, J = 8.2 Hz, 1H), 7.71 (d, J = 8.8 Hz, 2H), 8.16 (d, J =8.8 Hz, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 0.94 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.73 (s, 1H), 3.85 (s, 3H), 4.89 (d, J = 13.7 Hz, 1H), 5.23 (d,J = 13.7 Hz, 1H), 6.08 (dd, J = 11.1, 2.4 Hz, 1H), 6.40 (td, J = 8.3,2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.88-6.92 (m, 2H), 6.90 (d, J =8.1 Hz, 1H), 6.98 (dd, J = 8.2, 2.2 Hz, 1H), 7.37 (d, J = 8.2 Hz, 1H),7.71-7.73 (m, 2H), 7.85-7.87 (m, 1H), 8.01-8.04 (m, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.97 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.73 (s, 1H), 3.83 (s, 3H), 4.87 (d, J = 13.4 Hz, 1H), 5.21 (d,J = 13.4 Hz, 1H), 6.09 (dd, J = 11.3, 2.4 Hz, 1H), 6.40 (td, J = 8.2,2.4 Hz, 1H), 6.74 (d, J = 7.9 Hz, 1H), 6.89-6.92 (m, 1H), 6.93 (d, J =7.9 Hz, 1H), 6.94 (d, J = 2.1 Hz, 1H), 7.00 (dd, J = 8.2, 2.1 Hz, 1H),7.37 (d, J = 8.2 Hz, 1H), 7.59 (ddd, J = 7.8, 4.8, 1.1 Hz, 1H), 7.95(td, J = 7.8, 1.8 Hz, 1H), 8.31 (dt, J = 7.8, 1.1 Hz, 1H), 8.87 (ddd, J= 4.8, 1.8, 1.1 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 3.47(s, 3H), 3.74 (s, 1H), 3.85 (s, 3H), 4.88 (d, J = 13.5 Hz, 1H), 5.23 (d,J = 13.5 Hz, 1H), 6.09 (dd, J = 11.2, 2.5 Hz, 1H), 6.41 (td, J = 8.2,2.5 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.90-6.93 (m, 1H), 6.90 (d, J =2.3 Hz, 1H), 6.92 (d, J = 8.1 Hz, 1H), 6.96 (dd, J = 8.2, 2.3 Hz, 1H),7.38 (d, J = 8.2 Hz, 1H), 7.50 (ddd, J = 8.0, 4.8, 0.9 Hz, 1H), 8.49(dt, J = 8.0, 2.0 Hz, 1H), 8.88 (dd, J = 4.8, 2.0 Hz, 1H), 9.43 (dd, J =2.0, 0.9 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 3.47(s, 3H), 3.75 (s, 1H), 3.84 (s, 3H), 4.87 (d, J = 13.5 Hz, 1H), 5.22 (d,J = 13.5 Hz, 1H), 6.09 (dd, J = 11.2, 2.4 Hz, 1H), 6.41 (td, J = 8.3,2.4 Hz, 1H), 6.74 (d, J = 7.8 Hz, 1H), 6.89 (d, J = 2.3 Hz, 1H),6.90-6.93 (m, 1H), 6.92 (d, J = 7.8 Hz, 1H), 6.95 (dd, J = 8.1, 2.3 Hz,1H), 7.38 (d, J = 8.1 Hz, 1H), 8.04 (dd, J = 4.3, 1.6 Hz, 2H), 8.89 (dd,J = 4.3, 1.6 Hz, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 0.95 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.73 (s, 1H), 3.83 (s, 3H), 4.87 (d, J = 13.4 Hz, 1H), 5.22 (d,J = 13.4 Hz, 1H), 6.08 (dd, J = 11.0, 2.4 Hz, 1H), 6.40 (td, J = 8.2,2.4 Hz, 1H), 6.73 (d, J = 8.2 Hz, 1H), 6.85 (d, J = 2.1 Hz, 1H),6.89-6.92 (m, 4H), 7.34 (d, J = 3.2 Hz, 1H), 7.53 (t, J = 1.7 Hz, 1H),8.23 (dd, J = 1.7, 0.6 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.27 (s, 3H), 1.31-1.44 (m, 3H),1.60-1.73 (m, 3H), 1.83-1.87 (m, 2H), 2.01 (s, 3H), 2.08-2.11 (m, 2H),2.59 (tt, J = 11.2, 3.7 Hz, 1H), 3.46 (s, 3H), 3.71 (s, 1H), 3.81 (s,3H), 4.85 (d, J = 13.6 Hz, 1H), 5.21 (d, J = 13.6 Hz, 1H), 6.05 (dd, J =11.1, 2.5 Hz, 1H), 6.39 (td, J = 8.3, 2.5 Hz, 1H), 6.71 (d, J = 8.2 Hz,1H), 6.73 (d, J = 2.2 Hz, 1H), 6.79 (dd, J = 8.2, 2.2 Hz, 1H), 6.88 (d,J = 8.1 Hz, 1H), 6.87- 6.91 (m, 1H), 7.30 (d, J = 8.1 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.26 (s, 3H), 2.00 (s, 3H), 3.45(s, 3H), 3.71 (s, 1H), 3.79 (s, 3H), 3.90 (s, 2H), 4.82 (d, J = 13.7 Hz,1H), 5.19 (d, J = 13.7 Hz, 1H), 6.04 (dd, J = 11.2, 2.4 Hz, 1H), 6.38(td, J = 8.3, 2.4 Hz, 1H), 6.70 (d, J = 8.2 Hz, 1H), 6.73 (d, J = 2.2Hz, 1H), 6.79 (dd, J = 8.2, 2.2 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H),6.88-6.91 (m, 1H), 7.29 (d, J = 8.2 Hz, 1H), 7.30-7.43 (m, 5H)

¹H-NMR (500 MHz, CDCl₃) δ 0.94 (s, 3H), 1.26 (s, 3H), 2.01 (s, 3H), 2.93(t, J = 7.6 Hz, 2H), 3.11 (t, J = 7.6 Hz, 2H), 3.46 (s, 3H), 3.71 (s,1H), 3.78 (s, 3H), 4.84 (d, J = 13.7 Hz, 1H), 5.19 (d, J = 13.7 Hz, 1H),6.05 (dd, J = 11.3, 2.4 Hz, 1H), 6.39 (td, J = 8.2, 2.4 Hz, 1H), 6.62(d, J = 2.4 Hz, 1H), 6.71 (d, J = 7.9 Hz, 1H), 6.74 (dd, J = 8.1, 2.4Hz, 1H), 6.87 (d, J = 7.9 Hz, 1H), 6.83-6.91 (m, 1H), 7.24- 7.36 (m, 6H)

¹H-NMR (500 MHz, DMSO-d₆) δ 0.81 (s, 3H), 1.07 (s, 3H), 1.93 (s, 3H),3.33 (s, 3H), 3.80 (s, 3H), 4.86 (d, J = 14.0 Hz, 1H), 5.23 (d, J = 14.0Hz, 1H), 6.15 (dd, J = 11.1, 2.4 Hz, 1H), 6.15 (s, 1H), 6.50 (td, J =8.3. 2.4 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H), 6.82 (dd, J = 3.7, 1.7 Hz,1H), 6.85 (d, J = 8.1 Hz, 1H), 6.97 (dd, J = 8.3, 2.1 Hz, 1H), 6.99-7.02 (m, 1H), 7.10 (d, J = 2.1 Hz, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.59(dd, J = 3.7, 0.8 Hz, 1H), 8.13 (dd, J = 1.7, 0.8 Hz, 1H)

¹H-NMR (400 MHz, DMSO-d₆) δ 0.86 (s, 3H), 1.07 (s, 3H), 1.92 (s, 3H),2.29 (s, 3H), 3.32 (s, 3H), 3.78 (s, 3H), 4.83 (d, J = 14.0 Hz, 1H),5.21 (d, J = 14.0 Hz, 1H), 6.12 (dd, J = 11.5, 2.5 Hz, 1H), 6.14 (s,1H), 6.49 (td, J = 8.3, 2.5 Hz, 1H), 6.79 (d, J = 8.0 Hz, 1H), 6.82 (d,J = 8.0 Hz, 1H), 6.83 (dd, J = 8.2, 2.2 Hz, 1H), 6.93 (d, J = 2.2 Hz,1H), 6.98- 7.01 (m, 1H), 7.27 (d, J = 8.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.92 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 3.48(s, 3H), 3.72 (s, 1H), 3.89 (s, 3H), 4.87 (d, J = 13.6 Hz, 1H), 5.25 (d,J = 13.6 Hz, 1H), 6.06 (dd, J = 11.2, 2.4 Hz, 1H), 6.39 (td, J = 8.3,2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.88-6.91 (m, 1H), 6.90 (d, J =8.1 Hz, 1H), 7.07 (dd, J = 8.1, 2.0 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H),7.50-7.61 (m, 3H), 7.77 (d, J = 2.0 Hz, 1H), 7.89-7.92 (m, 3H)

¹H-NMR (400 MHz, CDCl₃) δ 0.91 (s, 3H), 1.29 (s, 3H), 2.01 (s, 3H), 2.22(s, 3H), 3.46 (s, 3H), 3.70 (s, 1H), 3.84 (s, 3H), 4.84 (d, J = 13.4 Hz,1H), 5.22 (d, J = 13.4 Hz, 1H), 6.04 (dd, J = 11.2, 2.5 Hz, 1H), 6.38(td, J = 8.2, 2.5 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.87 (d, J = 8.1Hz, 1H), 6.87-6.91 (m, 1H), 6.92 (dd, J = 8.2, 1.8 Hz, 1H), 7.24 (d, J =8.2 Hz, 1H), 7.58 (d, J = 1.8 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.92 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 3.48(s, 3H), 3.71 (s, 1H), 3.91 (s, 3H), 4.88 (d, J = 13.7 Hz, 1H), 5.25 (d,J = 13.7 Hz, 1H), 6.07 (dd, J = 11.2, 2.4 Hz, 1H), 6.38 (td, J = 8.2,2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.87-6.91 (m, 1H), 6.92 (d, J =8.1 Hz, 1H), 7.25 (dd, J = 8.2, 2.2 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H),7.52 (ddd, J = 7.7, 4.7, 1.1 Hz, 1H), 7.85 (d, J = 2.2 Hz, 1H), 7.94(td, J = 7.7, 1.7 Hz, 1H), 8.32 (dt, J = 7.7, 1.1 Hz, 1H), 8.65 (ddd, J= 4.7, 1.7, 1.1 Hz, 1H), 10.16 (s, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.94 (s, 3H), 1.30 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.73 (s, 1H), 3.89 (s, 3H), 4.86 (d, J = 13.6 Hz, 1H), 5.24 (d,J = 13.6 Hz, 1H), 6.07 (dd, J = 11.2, 2.4 Hz, 1H), 6.39 (td, J = 8.3,2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.89-6.92 (m, 1H), 6.90 (d, J =8.1 Hz, 1H), 7.10 (dd, J = 8.1, 1.9 Hz, 1H), 7.33 (d, J = 8.1 Hz, 1H),7.49 (ddd, J = 7.9, 4.8, 1.5 Hz, 1H), 7.71 (d, J = 1.9 Hz, 1H), 7.91 (s,1H), 8.24 (dt, J = 7.9, 1.5 Hz, 1H), 8.82 (dd, J = 4.8, 1.5 Hz, 1H),9.13 (d, J = 1.5 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.94 (s, 3H), 1.30 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.73 (s, 1H), 3.89 (s, 3H), 4.85 (d, J = 13.6 Hz, 1H), 5.23 (d,J = 13.6 Hz, 1H), 6.06 (dd, J = 11.2, 2.4 Hz, 1H), 6.40 (td, J = 8.2,2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.90 (d, J = 8.1 Hz, 1H),6.89-6.92 (m, 1H), 7.09 (dd, J = 8.3, 2.1 Hz, 1H), 7.33 (d, J = 8.3 Hz,1H), 7.71 (d, J = 2.1 Hz, 1H), 7.74 (dd, J = 4.4 Hz, 2H), 7.95 (s, 1H),8.84 (dd, J = 4.4 Hz, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 0.92 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.71 (s, 1H), 3.89 (s, 3H), 4.87 (d, J = 14.0 Hz, 1H), 5.25 (d,J = 14.0 Hz, 1H), 6.07 (dd, J = 10.9, 2.4 Hz, 1H), 6.39 (td, J = 8.4,2.4 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H), 6.88-6.92 (m, 1H), 6.90 (d, J =8.1 Hz, 1H), 7.06 (dd, J = 8.2, 1.9 Hz, 1H), 7.31 (d, J = 8.2 Hz, 1H),7.39-7.52 (m, 2H), 7.43 (td, J = 7.6, 2.0 Hz, 1H), 7.74 (d, J = 1.9 Hz,1H), 7.81 (dd, J = 7.6, 2.0 Hz, 1H), 7.97 (br s, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.92 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.71 (s, 1H), 3.88 (s, 3H), 3.89 (s, 3H), 4.87 (d, J = 13.8 Hz,1H), 5.24 (d, J = 13.8 Hz, 1H), 6.06 (dd, J = 11.2, 2.4 Hz, 1H), 6.38(td, J = 8.2, 2.4 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 6.88- 6.91 (m, 1H),6.90 (d, J = 8.0 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 7.04 (dd, J = 8.1,2.1 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.76 (d, J = 2.1 Hz, 1H), 7.83(s, 1H), 7.87 (d, J = 8.8 Hz, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 0.93 (s, 3H), 1.27 (s, 3H), 1.35 (d, J = 7.0Hz, 6H), 2.01 (s, 3H), 2.84 (sept, J = 7.0 Hz, 1H), 3.46 (s, 3H), 3.71(s, 1H), 3.82 (s, 3H), 4.85 (d, J = 13.7 Hz, 1H), 5.21 (d, J = 13.7 Hz,1H), 6.06 (dd, J = 11.0, 2.4 Hz, 1H), 6.39 (td, J = 8.4, 2.4 Hz, 1H),6.71 (d, J = 8.1 Hz, 1H), 6.74 (d, J = 2.2 Hz, 1H), 6.80 (dd, J = 8.2,2.2 Hz, 1H), 6.88- 6.91 (m, 1H), 6.89 (d, J = 8.1 Hz, 1H), 7.31 (d, J =8.2 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.95 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.72 (s, 1H), 3.83 (s, 3H), 4.88 (d, J = 13.4 Hz, 1H), 5.23 (d,J = 13.4 Hz, 1H), 6.08 (dd, J = 11.3, 2.4 Hz, 1H), 6.40 (td, J = 8.2,2.4 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H), 6.88 (d, J = 2.1 Hz, 1H),6.89-6.92 (m, 1H), 6.91 (d, J = 7.9 Hz, 1H), 6.93 (dd, J = 8.3, 2.1 Hz,1H), 7.35 (d, J = 8.3 Hz, 1H), 7.41 (dd, J = 5.0, 3.1 Hz, 1H), 7.69 (dd,J = 5.0, 1.2 Hz, 1H), 8.35 (dd, J = 3.1, 1.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.27 (s, 3H), 1.39 (s, 9H), 2.01(s, 3H), 3.46 (s, 3H), 3.71 (br s, 1H), 3.82 (s, 3H), 4.85 (d, J = 13.7Hz, 1H), 5.21 (d, J = 13.7 Hz, 1H), 6.06 (dd, J = 11.2, 2.4 Hz, 1H),6.39 (td, J = 8.3, 2.4 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.72 (d, J =2.1 Hz, 1H), 6.79 (dd, J = 3.3, 2.1 Hz, 1H), 6.87- 6.92 (m, 1H), 6.88(d, J = 8.1 Hz, 1H), 7.31 (d, J = 8.3 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.95 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.73 (br s, 1H), 3.84 (s, 3H), 4.88 (d, J = 13.7 Hz, 1H), 5.23(d, J = 13.7 Hz, 1H), 6.08 (dd, J = 11.0, 2.4 Hz, 1H), 6.40 (td, J =8.2, 2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.89-6.92 (m, 1H), 6.91 (d,J = 2.2 Hz, 1H), 6.92 (d, J = 8.1 Hz, 1H), 6.97 (dd, J = 8.2, 2.2 Hz,1H), 7.22-7.26 (m, 1H), 7.31 (td, J = 7.6, 0.9 Hz, 1H), 7.37 (d, J = 8.2Hz, 1H), 7.61-7.65 (m, 1H), 8.14 (td, J = 7.6, 1.8 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 3.48(s, 3H), 3.64-3.85 (m, 1H), 3.84 (s, 3H), 4.88 (d, J = 13.6 Hz, 1H),5.23 (d, J = 13.6 Hz, 1H), 6.09 (dd, J = 11.2, 2.4 Hz, 1H), 6.41 (td, J= 8.3, 2.4 Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 6.88-6.94 (m, 1H), 6.89(d, J = 2.4 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 6.95 (dd, J = 8.3, 2.4Hz, 1H), 7.37 (tdd, J = 8.2, 2.7, 1.2 Hz, 1H), 7.37 (d, J = 8.3 Hz, 1H),7.52 (td, J = 8.2, 5.5 Hz, 1H), 7.90- 7.93 (m, 1H), 8.02-8.05 (m, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 3.48(s, 3H), 3.73 (s, 1H), 3.84 (s, 3H), 3.91 (s, 3H), 4.89 (d, J = 13.6 Hz,1H), 5.24 (d, J = 13.6 Hz, 1H), 6.09 (dd, J = 11.2, 2.4 Hz, 1H), 6.40(td, J = 8.3, 2.4 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.89- 6.96 (m, 1H),6.89 (d, J = 2.3 Hz, 1H), 6.93 (d, J = 8.1 Hz, 1H), 6.95 (dd, J = 8.2,2.3 Hz, 1H), 7.21 (dt, J = 8.1, 1.3 Hz, 1H), 7.37 (d, J = 8.2 Hz, 1H),7.45 (t, J = 8.1 Hz, 1H), 7.73- 7.74 (m, 1H), 7.83-7.85 (m, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.94 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 3.47(s, 3H), 3.73 (s, 1H), 3.83 (s, 3H), 3.91 (s, 3H), 4.89 (d, J = 13.6 Hz,1H), 5.23 (d, J = 13.6 Hz, 1H), 6.09 (dd, J = 11.2, 2.4 Hz, 1H), 6.40(td, J = 8.3, 2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.88-6.95 (m, 1H),6.88 (d, J = 2.2 Hz, 1H), 6.92 (d, J = 8.1 Hz, 1H), 6.93 (dd, J = 8.2,2.2 Hz, 1H), 7.01 (dt, J = 9.5, 2.4 Hz, 2H), 7.36 (d, J = 8.2 Hz, 1H),8.18 (dt, J = 9.5, 2.4 Hz, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 0.97 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 3.47(s, 3H), 3.75 (s, 1H), 3.85 (s, 3H), 4.87 (d, J = 13.4 Hz, 1H), 5.22 (d,J = 13.4 Hz, 1H), 6.09 (dd, J = 11.2, 2.4 Hz, 1H), 6.41 (td, J = 8.3,2.4 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.90 (d, J = 2.4 Hz, 1H),6.91-6.93 (m, 1H), 6.92 (d, J = 8.1 Hz, 1H), 6.96 (dd, J = 8.0, 2.4 Hz,1H), 7.39 (d, J = 8.0 Hz, 1H), 8.37-8.43 (m, 4H)

¹H-NMR (400 MHz, CDCl₃) δ 0.94 (s, 3H), 1.27 (s, 3H), 1.30 (t, J = 7.6Hz, 3H), 2.01 (s, 3H), 2.63 (q, J = 7.6 Hz, 2H), 3.46 (s, 3H), 3.71 (s,1H), 3.81 (s, 3H), 4.85 (d, J = 13.7 Hz, 1H), 5.20 (d, J = 13.7 Hz, 1H),6.06 (dd, J = 11.1, 2.4 Hz, 1H), 6.39 (td, J = 8.3, 2.4 Hz, 1H), 6.71(d, J = 8.0 Hz, 1H), 6.75 (d, J = 2.1 Hz, 1H), 6.81 (dd, J = 8.1, 2.1Hz, 1H), 6.88-6.92 (m, 1H), 6.89 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.1Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.94 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.46(s, 3H), 3.72 (s, 1H), 3.82 (s, 3H), 4.86 (d, J = 13.6 Hz, 1H), 5.21 (d,J = 13.6 Hz, 1H), 6.05 (dd, J = 10.5, 1.2 Hz, 1H), 6.07 (dd, J = 11.2,2.4 Hz, 1H), 6.35 (dd, J = 17.3, 10.5 Hz, 1H), 6.39 (td, J = 8.4, 2.4Hz, 1H), 6.65 (dd, J = 17.3, 1.2 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H), 6.80(d, J = 2.1 Hz, 1H), 6.89 (dd, J = 8.1, 2.1 Hz, 1H), 6.89- 6.91 (m, 1H),6.89 (d, J = 8.1 Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.95 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.73 (s, 1H), 3.84 (s, 3H), 4.87 (d, J = 13.6 Hz, 1H), 5.22 (d,J = 13.6 Hz, 1H), 6.08 (dd, J = 11.3, 2.4 Hz, 1H), 6.40 (td, J = 8.2,2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.89-6.90 (m, 1H), 6.90 (d, J =2.1 Hz, 1H), 6.91 (d, J = 8.1 Hz, 1H), 6.95 (dd, J = 8.1, 2.1 Hz, 1H),7.19-7.21 (m, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.70 (d, J = 4.9 Hz, 1H),8.01 (d, J = 3.7 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.94 (s, 3H), 1.27 (s, 3H), 2.01 (s, 3H), 3.46(s, 3H), 3.73 (s, 1H), 3.82 (s, 3H), 3.94 (s, 3H), 4.84 (d, J = 13.5 Hz,1H), 5.20 (d, J = 13.5 Hz, 1H), 6.05 (dd, J = 11.2, 2.4 Hz, 1H), 6.39(td, J = 8.3, 2.4 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H), 6.84 (d, J = 2.2Hz, 1H), 6.87-6.92 (m, 3H), 7.31 (d, J = 8.3 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.27 (s, 3H), 2.01 (s, 3H), 3.46(s, 3H), 3.73 (s, 1H), 3.84 (s, 3H), 4.85 (d, J = 13.6 Hz, 1H), 5.20 (d,J = 13.6 Hz, 1H), 6.06 (dd, J = 11.2, 2.4 Hz, 1H), 6.39 (td, J = 8.3,2.4 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H), 6.89 (d, J = 7.9 Hz, 1H),6.88-6.92 (m, 1H), 6.95 (d, J = 2.3 Hz, 1H), 7.00 (dd, J = 8.2, 2.3 Hz,1H), 7.28-7.32 (m, 3H), 7.34 (d, J = 8.2 Hz, 1H) 7.41-7.46 (m, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 0.92 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.71 (s, 1H), 3.83 (s, 3H), 4.85 (d, J = 13.7 Hz, 1H), 5.22 (d,J = 13.7 Hz, 1H), 6.05 (dd, J = 11.2, 2.4 Hz, 1H), 6.39 (td, J = 8.3,2.4 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.89 (d, J = 8.1 Hz, 1H),6.89-6.91 (m, 2H), 7.10 (br s, 1H), 7.21 (dd, J = 8.5, 1.2 Hz, 2H),7.25- 7.28 (m, 2H), 7.40-7.44 (m, 2H), 7.52 (br s, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, H), 2.47 (s, 3H), 3.46 (s, 3H), 3.78 (s, 4H), 5.13 (d, J = 13.2 Hz,1H), 5.31 (d, J = 13.2 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.77 (d, J =8.0 Hz, 1H), 6.85 (d, J = 2.3 Hz, 1H), 6.89 (dd, J = 8.2, 2.3 Hz, 1H),6.89 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.39-7.43 (m, 1H),7.45 (d, J = 3.7 Hz, 1H), 7.49-7.56 (m, 2H), 8.07 (ddd, J = 7.8, 1.7,0.5 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.77 (s, 3H), 3.79 (s, 1H), 5.14 (d, J = 13.3 Hz, 1H), 5.31 (d,J = 13.3 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H),6.83 (d, J = 2.3 Hz, 1H), 6.86 (dd, J = 8.1, 2.3 Hz, 1H), 6.91 (d, J =7.9 Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.45 (d, J = 3.7 Hz, 1H), 7.53(t, J = 7.8 Hz, 2H), 7.66 (t, J = 7.8 Hz, 1H), 8.22 (d, J = 7.8 Hz, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.77 (s, 3H), 3.82 (s, 1H), 5.13 (d, J = 13.3 Hz, 1H), 5.30 (d,J = 13.3 Hz, 1H), 6.70 (d, J = 3.8 Hz, 1H), 6.78 (d, J = 7.9 Hz, 1H),6.82 (d, J = 2.4 Hz, 1H), 6.87 (dd, J = 8.2, 2.4 Hz, 1H), 6.90 (d, J =7.9 Hz, 1H), 7.34 (d, J = 8.2 Hz, 1H), 7.45 (d, J = 3.8 Hz, 1H), 8.02(dd, J = 4.4, 1.6 Hz, 2H), 8.88 (dd, J = 4.4, 1.6 Hz, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.45(s, 3H), 3.76 (s, 3H), 3.79 (s, 1H), 5.11 (d, J = 13.4 Hz, 1H), 5.30 (d,J = 13.4 Hz, 1H), 6.61 (d, J = 3.5 Hz, 1H), 6.70 (dd, J = 3.8 Hz, 1H),6.76 (d, J = 7.9 Hz, 1H), 6.82 (d, J = 2.3 Hz, 1H), 6.86 (dd, J = 8.2,2.3 Hz, 1H), 6.89 (d, J = 7.9 Hz, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.40(dd, J = 3.5, 0.9 Hz, 1H), 7.44 (d, J = 3.8 Hz, 1H), 7.69 (dd, J = 1.7,0.9 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.76 (s, 3H), 3.77 (s, 1H), 5.13 (d, J = 13.4 Hz, 1H), 5.30 (d,J = 13.4 Hz, 1H), 6.70 (d, J = 3.6 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H),6.81 (d, J = 2.1 Hz, 1H), 6.84 (dd, J = 8.3, 2.1 Hz, 1H), 6.90 (d, J =7.9 Hz, 1H), 7.31 (d, J = 8.3 Hz, 1H), 7.40 (dd, J = 5.3, 3.1 Hz, 1H),7.45 (d, J = 3.6 Hz, 1H), 7.68 (dd, J = 5.3, 0.9 Hz, 1H), 8.33 (dd, J =3.1, 0.9 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.76 (s, 3H), 3.79 (s, 1H), 5.12 (d, J = 13.3 Hz, 1H), 5.30 (d,J = 13.3 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H),6.79 (d, J = 2.1 Hz, 1H), 6.82 (dd, J = 8.1, 2.1 Hz, 1H), 6.89-6.90 (m,1H), 6.90 (d, J = 7.9 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.45 (d, J =3.7 Hz, 1H), 7.51-7.52 (m, 1H), 8.21- 8.22 (m, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.77 (s, 3H), 3.80 (s, 1H), 5.13 (d, J = 13.3 Hz, 1H), 5.31 (d,J = 13.3 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.77 (d, J = 8.1 Hz, 1H),6.84 (d, J = 2.4 Hz, 1H), 6.88 (dd, J = 8.5, 2.4 Hz, 1H), 6.90 (d, J =8.1 Hz, 1H), 7.21-7.26 (m, 1H), 7.30 (t, J = 7.6 Hz, 1H), 7.32 (d, J =8.5 Hz, 1H), 7.45 (d, J = 3.7 Hz, 1H), 7.60-7.64 (m, 1H), 8.12 (td, J =7.6, 1.7 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.77 (s, 3H), 3.80 (s, 1H), 5.13 (d, J = 13.4 Hz, 1H), 5.30 (d,J = 13.4 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H),6.81 (d, J = 2.2 Hz, 1H), 6.85 (dd, J = 8.2, 2.2 Hz, 1H), 6.90 (d, J =7.9 Hz, 1H), 7.32 (d, J = 8.2 Hz, 1H), 7.45 (d, J = 3.7 Hz, 1H), 7.51(d, J = 8.6 Hz, 2H), 8.15 (d, J = 8.6 Hz, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 2.70(s, 3H), 3.46 (s, 3H), 3.77 (s, 3H), 3.80 (s, 1H), 5.14 (d, J = 13.3 Hz,1H), 5.31 (d, J = 13.3 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.77 (d, J =8.1 Hz, 1H), 6.81 (d, J = 2.2 Hz, 1H), 6.85 (dd, J = 8.2, 2.2 Hz, 1H),6.90 (d, J = 8.1 Hz, 1H), 7.32-7.36 (m, 2H), 7.33 (d, J = 8.2 Hz, 1H),7.45 (d, J = 3.7 Hz, 1H), 7.50 (td, J = 7.9, 1.5 Hz, 1H), 8.18 (d, J =7.9 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.48 (s, 3H), 3.46(s, 3H), 3.78 (s, 3H), 3.81 (s, 1H), 5.13 (d, J = 13.3 Hz, 1H), 5.30 (d,J = 13.3 Hz, 1H), 6.70 (d, J = 3.6 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H),6.83 (d, J = 2.2 Hz, 1H), 6.87 (dd, J = 8.2, 2.2 Hz, 1H), 6.91 (d, J =8.1 Hz, 1H), 7.34 (d, J = 8.2 Hz, 1H), 7.45 (d, J = 3.6 Hz, 1H), 7.49(ddd, J = 8.0, 4.9, 0.9 Hz, 1H), 8.47 (dt, J = 8.0, 1.9 Hz, 1H), 8.87(dd, J = 4.9, 1.9 Hz, 1H), 9.42 (dd, J = 1.9, 0.9 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.77 (s, 3H), 3.79 (s, 1H), 3.96 (s, 3H), 5.13 (d, J = 13.4 Hz,1H), 5.31 (d, J = 13.4 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.77 (d, J =7.9 Hz, 1H), 6.84 (d, J = 2.2 Hz, 1H), 6.87 (dd, J = 8.2, 2.2 Hz, 1H),6.90 (d, J = 7.9 Hz, 1H), 7.05-7.08 (m, 2H), 7.31 (d, J = 8.2 Hz, 1H),7.45 (d, J = 3.7 Hz, 1H), 7.56 (ddd, J = 8.7, 6.9, 1.8 Hz, 1H), 8.04(dd, J = 7.8, 1.8 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.06 (t, J = 7.5 Hz, 3H), 1.20 (s, 3H), 1.42(s, 3H), 1.80 (qt, J = 7.5, 7.4 Hz, 2H), 2.47 (s, 3H), 2.56 (t, J = 7.4Hz, 2H), 3.44 (s, 3H), 3.74 (s, 3H), 3.78 (s, 1H), 5.10 (d, J = 13.4 Hz,1H), 5.28 (d, J = 13.4 Hz, 1H), 6.68 (d, J = 2.1 Hz, 1H), 6.69 (d, J =3.7 Hz, 1H), 6.72 (dd, J = 8.1, 2.1 Hz, 1H), 6.75 (d, J = 8.1 Hz, 1H),6.87 (d, J = 8.1 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.43 (d, J = 3.7 Hz,1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.20 (s, 3H), 1.33 (d, J = 7.0 Hz, 6H), 1.42(s, 3H), 2.47 (s, 3H), 2.79-2.84 (m, 1H), 3.45 (s, 3H), 3.75 (s, 3H),3.78 (s, 1H), 5.10 (d, J = 13.4 Hz, 1H), 5.28 (d, J = 13.4 Hz, 1H), 6.68(d, J = 2.1 Hz, 1H), 6.69 (d, J = 3.7 Hz, 1H), 6.72 (dd, J = 8.2, 2.1Hz, 1H), 6.75 (d, J = 7.9 Hz, 1H), 6.87 (d, J = 7.9 Hz, 1H), 7.26 (d, J= 8.2 Hz, 1H), 7.43 (d, J = 3.7 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.20 (s, 3H), 1.41 (s, 3H), 2.46 (s, 3H), 3.44(s, 3H), 3.72 (s, 3H), 3.77 (s, 1H), 3.88 (s, 2H), 5.08 (d, J = 13.3 Hz,1H), 5.27 (d, J = 13.3 Hz, 1H), 6.67 (d, J = 2.3 Hz, 1H), 6.68 (d, J =3.7 Hz, 1H), 6.71 (dd, J = 8.1, 2.3 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H),6.85 (d, J = 8.1 Hz, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.29- 7.34 (m, 1H),7.37-7.47 (m, 5H)

¹H-NMR (500 MHz, CDCl₃) δ 1.20 (s, 3H), 1.29-1.39 (m, 3H), 1.42 (s, 3H),1.57- 1.72 (m, 3H), 1.82-1.85 (m, 2H), 2.05-2.09 (m, 2H), 2.47 (s, 3H),2.55-2.60 (m, 1H), 3.41 (s, 3H), 3.74 (s, 3H), 3.78 (s, 1H), 5.10 (d, J= 13.3 Hz, 1H), 5.28 (d, J = 13.3 Hz, 1H), 6.67 (d, J = 2.2 Hz, 1H),6.69 (d, J = 3.8 Hz, 1H), 6.71 (dd, J = 8.1, 2.2 Hz, 1H), 6.75 (d, J =8.1 Hz, 1H), 6.87 (d, J = 8.1 Hz, 1H) 7.25- 7.26 (m, 1H), 7.43 (d, J =3.8 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.76 (s, 3H), 3.78 (s, 1H), 3.91 (s, 3H), 5.13 (d, J = 13.3 Hz,1H), 5.31 (d, J = 13.3 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.77 (d, J =8.1 Hz, 1H), 6.81 (d, J = 2.1 Hz, 1H), 6.84 (dd, J = 8.1, 2.1 Hz, 1H),6.91 (d, J = 8.1 Hz, 1H) 7.00 (d, J = 8.9 Hz, 2H), 7.31 (d, J = 8.1 Hz,1H), 7.45 (d, J = 3.7 Hz, 1H), 8.17 (d, J = 8.9 Hz, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.47(s, 3H), 3.77 (s, 3H), 3.80 (s, 1H), 5.13 (d, J = 13.1 Hz, 1H), 5.30 (d,J = 13.1 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H),6.83 (d, J = 2.1 Hz, 1H), 6.86 (dd, J = 8.3, 2.1 Hz, 1H), 6.90 (d, J =7.9 Hz, 1H) 7.20 (dd, J = 4.9, 3.7 Hz, 1H), 7.31 (d, J = 8.3 Hz, 1H),7.45 (d, J = 3.7 Hz, 1H), 7.68 (dd, J = 4.9, 1.2 Hz, 1H), 8.00 (dd, J =3.7, 1.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.21 (s, 3H), 1.41 (s, 3H), 2.47 (s, 3H), 3.45(s, 3H), 3.75 (s, 3H), 3.79 (s, 1H), 3.92 (s, 3H), 5.09 (d, J = 13.3 Hz,1H), 5.28 (d, J = 13.3 Hz, 1H), 6.69 (d, J = 3.8 Hz, 1H), 6.75 (d, J =8.1 Hz, 1H), 6.77 (d, J = 2.2 Hz, 1H), 6.82 (dd, J = 8.2, 2.2 Hz, 1H),6.86 (d, J = 8.1 Hz, 1H), 7.27 (d, J = 8.2 Hz, 1H), 7.43 (d, J = 3.8 Hz,1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.21 (s, 3H), 1.41 (s, 3H), 2.47 (s, 3H), 3.45(s, 3H), 3.76 (s, 3H), 3.80 (s, 1H), 5.11 (d, J = 13.3 Hz, 1H), 5.29 (d,J = 13.3 Hz, 1H), 6.69 (d, J = 3.8 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H),6.87 (d, J = 8.1 Hz, 1H), 6.89 (d, J = 2.2 Hz, 1H), 6.92 (dd, J = 8.2,2.2 Hz, 1H), 7.27-7.31 (m, 4H), 7.40-7.45 (m, 3H)

¹H-NMR (400 MHz, CDCl₃) δ 0.92 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.71 (s, 1H), 3.88 (s, 3H), 4.86 (d, J = 13.6 Hz, 1H), 5.24 (d,J = 13.6 Hz, 1H), 6.06 (dd, J = 11.2, 2.4 Hz, 1H), 6.38 (td, J = 8.3,2.4 Hz, 1H), 6.59 (dd, J = 3.5, 1.8 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H),6.87-6.91 (m, 1H), 6.90 (d, J = 8.1 Hz, 1H), 7.07 (dd, J = 8.3, 2.1 Hz,1H), 7.27 (dd, J = 3.5, 0.9 Hz, 1H), 7.30 (d, J = 8.3 Hz, 1H), 7.55 (dd,J = 1.8, 0.9 Hz, 1H), 7.75 (d, J = 2.1 Hz, 1H), 8.17 (s, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.92 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 2.55(s, 3H), 3.47 (s, 3H), 3.71 (s, 1H), 3.88 (s, 3H), 4.87 (d, J = 13.6 Hz,1H), 5.24 (d, J = 13.6 Hz, 1H), 6.07 (dd, J = 11.2, 2.4 Hz, 1H), 6.39(td, J = 8.2, 2.4 Hz, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.89-6.92 (m, 1H),6.89 (d, J = 7.9 Hz, 1H), 7.02 (d, J = 7.3 Hz, 1H), 7.29 (t, J = 7.6 Hz,1H), 7.30 (d, J = 7.6 Hz, 1H), 7.30 (d, J = 7.3 Hz, 1H), 7.38- 7.41 (m,1H), 7.52 (d, J = 7.6 Hz, 1H), 7.55 (s, 1H), 7.72 (s, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.92 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 3.48(s, 3H), 3.71 (s, 1H), 3.89 (s, 3H), 4.87 (d, J = 13.7 Hz, 1H), 5.24 (d,J = 13.7 Hz, 1H), 6.07 (dd, J = 11.0, 2.4 Hz, 1H), 6.39 (td, J = 8.2,2.4 Hz, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.88-6.91 (m, 1H), 6.90 (d, J =7.9 Hz, 1H), 7.10 (dd, J = 8.0, 2.1 Hz, 1H), 7.22 (dd, J = 11.9, 7.9 Hz,1H), 7.31 (d, J = 8.0 Hz, 1H), 7.33-7.37 (m, 1H), 7.53-7.58 (m, 1H),7.76 (d, J = 2.1 Hz, 1H), 8.19-8.22 (m, 1H), 8.55- 8.58 (m, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.89 (s, 3H), 1.30 (s, 3H), 2.02 (s, 3H), 3.48(s, 3H), 3.70 (s, 1H), 3.90 (s, 3H), 4.10 (s, 3H), 4.89 (d, J = 13.7 Hz,1H), 5.27 (d, J = 13.7 Hz, 1H), 6.06 (dd, J = 11.3, 2.4 Hz, 1H), 6.38(td, J = 8.2, 2.4 Hz, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.88-6.90 (m, 1H),6.91 (d, J = 7.9 Hz, 1H), 7.00 (dd, J = 8.0, 1.9 Hz, 1H), 7.07 (d, J =7.9 Hz, 1H), 7.15-7.18 (m, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.53 (ddd, J =8.6, 7.3, 1.7 Hz, 1H), 7.91 (d, J = 1.9 Hz, 1H), 8.31 (dd, J = 7.3, 1.7Hz, 1H), 9.94 (s, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.92 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.71 (s, 1H), 3.88 (s, 3H), 4.88 (d, J = 13.4 Hz, 1H), 5.24 (d,J = 13.4 Hz, 1H), 6.07 (dd, J = 11.3, 2.4 Hz, 1H), 6.39 (td, J = 8.4,2.4 Hz, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.88-6.91 (m, 1H), 6.89 (d, J =7.9 Hz, 1H), 7.02 (dd, J = 8.0, 1.9 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H),7.54 (s, 1H), 7.61- 7.64 (m, 1H), 7.66 (d, J = 1.9 Hz, 1H), 7.68-7.71(m, 2H), 7.79 (d, J = 7.6 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.29 (s, 3H), 2.03 (s, 3H), 3.48(s, 3H), 3.73 (s, 1H), 3.88 (s, 3H), 4.88 (d, J = 13.7 Hz, 1H), 5.25 (d,J = 13.7 Hz, 1H), 6.08 (dd, J = 11.0, 2.3 Hz, 1H), 6.40 (td, J = 8.3,2.3 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.89- 6.93 (m, 1H), 6.90 (d, J =8.1 Hz, 1H), 7.04 (dd, J = 8.1, 1.7 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H),7.62 (s, 1H), 7.65-7.70 (m, 3H), 7.77 (t, J = 7.6 Hz, 1H), 8.17 (d, J =8.0 Hz, 1H)

Example 158-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(3-methoxycarbonylbenzoyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 15-1)

A mixture of8-(5-fluoro-2-methylphenoxymethyl)-7-(4-hydroxy-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 11, 25.3 mg, 0.0562 mmol), monomethyl isophthalate (20.5mg, 0.114 mmol), N,N-diisopropylethylamine (38.8 μL, 0.223 mmol) andO-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate (43.4 mg, 0.114 mmol) was dissolved in anhydrousN,N-dimethylformamide (0.5 mL) and the reaction mixture was stirred atroom temperature overnight. The mixture was diluted with ethyl acetate(15 mL). The mixture was washed with water (15 mL) and saturated brine(15 mL) successively, dried over anhydrous magnesium sulfate, and thenthe solvent was removed under reduced pressure. The obtained residue waspurified by silica gel column chromatography (hexane-ethyl acetate) togive the titled compound (22.0 mg) as a colorless solid. (Yield 64%)

¹H-NMR (500 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 3.47(s, 3H), 3.73 (br s, 1H), 3.84 (s, 3H), 3.99 (s, 3H), 4.89 (d, J = 13.6Hz, 1H), 5.23 (d, J = 13.6 Hz, 1H), 6.10 (dd, J = 11.3, 2.4 Hz, 1H),6.41 (td, J = 8.2, 2.4 Hz, 1H), 6.74 (d, J = 7.9 Hz, 1H), 6.90- 6.93 (m,1H), 6.90 (d, J = 2.4 Hz, 1H), 6.92 (d, J = 7.9 Hz, 1H), 6.97 (dd, J =8.2, 2.4 Hz, 1H), 7.38 (d, J = 8.2 Hz, 1H), 7.64 (t, J = 7.8 Hz, 1H),8.33 (dt, J = 7.8, 1.5 Hz, 1H), 8.41 (dt, J = 7.8, 1.5 Hz, 1H), 8.89 (t,J = 1.5 Hz, 1H)Using any compounds among Compounds No. 8-2, 11, 13-2 and availablecompounds, the following Compounds (No. 15-2˜15-32) were obtained by amethod similar to that of Compound No. 15-1.

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 2.96(s, 3H), 3.47 (s, 3H), 3.74 (s, 1H), 3.85 (s, 3H), 4.88 (d, J = 13.7 Hz,1H), 5.23 (d, J = 13.7 Hz, 1H), 6.09 (dd, J = 11.2, 2.4 Hz, 1H), 6.41(td, J = 8.3, 2.4 Hz, 1H), 6.74 (d, J = 8.2 Hz, 1H), 6.87 (d, J = 2.2Hz, 1H), 6.89-6.93 (m, 1H), 6.91 (d, J = 8.2 Hz, 1H), 6.94 (dd, J = 8.2,2.2 Hz, 1H), 7.33 (dd, J = 8.0, 4.8 Hz, 1H), 7.38 (d, J = 8.2 Hz, 1H),8.47 (dd, J = 8.0, 2.0 Hz, 1H), 8.72 (dd, J = 4.8, 2.0 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.95 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 2.47(s, 3H), 3.47 (s, 3H), 3.72 (br s, 1H), 3.83 (s, 3H), 4.87 (d, J = 13.6Hz, 1H), 5.22 (d, J = 13.6 Hz, 1H), 6.08 (dd, J = 11.3, 2.5 Hz, 1H),6.39 (td, J = 8.3, 2.5 Hz, 1H), 6.47 (d, J = 1.8 Hz, 1H), 6.73 (d, J =7.9 Hz, 1H), 6.88- 6.92 (m, 1H), 6.89 (d, J = 2.2 Hz, 1H), 6.91 (d, J =7.9 Hz, 1H), 6.94 (dd, J = 8.2, 2.2 Hz, 1H), 7.35 (d, J = 8.2 Hz, 1H),7.56 (d, J = 1.8 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.96 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 2.34(s, 3H), 3.47 (s, 3H), 3.73 (br s, 1H), 3.83 (s, 3H), 4.87 (d, J = 13.4Hz, 1H), 5.22 (d, J = 13.4 Hz, 1H), 6.08 (dd, J = 11.3, 2.5 Hz, 1H),6.40 (td, J = 8.3, 2.5 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.83 (d, J =2.4 Hz, 1H), 6.89-6.92 (m, 1H), 6.90 (dd, J = 7.6, 2.4 Hz, 1H), 6.91 (d,J = 8.1 Hz, 1H), 7.20 (d, J = 7.5 Hz, 1H), 7.35 (d, J = 7.6 Hz, 1H),7.42 (t, J = 7.5 Hz, 1H), 7.67 (td, J = 7.5, 1.6 Hz, 1H), 8.26 (dd, J =7.5, 1.6 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.97 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.75 (br s, 1H), 3.83 (s, 3H), 4.87 (d, J = 13.4 Hz, 1H), 5.21(d, J = 13.4 Hz, 1H), 6.09 (dd, J = 11.3, 2.4 Hz, 1H), 6.40 (td, J =8.4, 2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.89-6.92 (m, 1H), 6.92 (d,J = 8.1 Hz, 1H), 6.92 (d, J = 2.3 Hz, 1H), 6.98 (dd, J = 8.1, 2.3 Hz,1H), 7.36 (d, J = 8.1 Hz, 1H), 8.48 (d, J = 2.0 Hz, 1H), 8.96 (d, J =2.0 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.94 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 2.50(s, 3H), 3.47 (s, 3H), 3.72 (br s, 1H), 3.84 (s, 3H), 4.89 (d, J = 13.4Hz, 1H), 5.23 (d, J = 13.4 Hz, 1H), 6.08 (dd, J = 11.0, 2.4 Hz, 1H),6.39 (td, J = 8.2, 2.4 Hz, 1H), 6.73 (d, J = 7.8 Hz, 1H), 6.89-6.92 (m,1H), 6.90 (d, J = 2.4 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.96 (dd, J =8.2, 2.4 Hz, 1H), 7.24- 7.28 (m, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.36 (d,J = 7.9 Hz, 1H), 7.58 (t, J = 7.9 Hz, 1H), 8.28 (dd, J = 7.9, 1.7 Hz,1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.95 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 2.46(s, 3H), 3.46 (s, 3H), 3.72 (br s, 1H), 3.82 (s, 3H), 4.87 (d, J = 13.7Hz, 1H), 5.21 (d, J = 13.7 Hz, 1H), 6.08 (dd, J = 11.2, 2.4 Hz, 1H),6.23 (d, J = 3.4 Hz, 1H), 6.40 (td, J = 8.3, 2.4 Hz, 1H), 6.73 (d, J =8.0 Hz, 1H), 6.88 (t, J = 2.7 Hz, 1H), 6.88- 6.92 (m, 1H), 6.91 (d, J =8.0 Hz, 1H), 6.93 (dd, J = 8.3, 2.7 Hz, 1H), 7.33 (d, J = 3.4 Hz, 1H),7.34 (d, J = 8.3 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.97 (s, 3H), 1.28 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.74 (br s, 1H), 3.84 (s, 3H), 4.86 (d, J = 13.4 Hz, 1H), 5.21(d, J = 13.4 Hz, 1H), 6.08 (dd, J = 11.0, 2.5 Hz, 1H), 6.40 (td, J =8.4, 2.5 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H), 6.89 (d, J = 2.1 Hz, 1H),6.90-6.92 (m, 1H), 6.91 (d, J = 7.9 Hz, 1H), 6.95 (dd, J = 8.2, 2.1 Hz,1H), 7.37 (d, J = 8.2 Hz, 1H), 8.72 (d, J = 0.6 Hz, 1H), 9.07 (d, J =0.6 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3H), 2.02 (s, 3H), 2.69(s, 3H), 3.47 (s, 3H), 3.78 (s, 1H), 3.83 (s, 3H), 4.88 (d, J = 13.4 Hz,1H), 5.23 (d, J = 13.4 Hz, 1H), 6.09 (dd, J = 11.2, 2.4 Hz, 1H), 6.40(td, J = 8.3, 2.4 Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 6.89 (d, J = 2.3Hz, 1H), 6.89-6.93 (m, 1H), 6.92 (d, J = 8.0 Hz, 1H), 6.95 (dd, J = 8.2,2.3 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.37 (d, J = 8.2 Hz, 1H), 8.35(dd, J = 8.1, 1.9 Hz, 1H), 9.30 (d, J = 1.9 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.97 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 3.47(s, 3H), 3.75 (s, 1H), 3.85 (s, 3H), 4.87 (d, J = 13.4 Hz, 1H), 5.21 (d,J = 13.4 Hz, 1H), 6.09 (dd, J = 11.2, 2.4 Hz, 1H), 6.41 (td, J = 8.3,2.4 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.89 (d, J = 2.2 Hz, 1H),6.90-6.93 (m, 1H), 6.91 (d, J = 8.1 Hz, 1H), 6.96 (dd, J = 8.3, 2.2 Hz,1H), 7.39 (d, J = 8.3 Hz, 1H), 9.47 (s, 1H), 9.48 (s, 2H)

¹H-NMR (400 MHZ, CDCl₃) δ 0.96 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.74 (s, 1H), 3.82 (s, 3H), 4.86 (d, J = 13.5 Hz, 1H), 5.21 (d,J = 13.5 Hz, 1H), 6.08 (dd, J = 11.3, 2.4 Hz, 1H), 6.40 (td, J = 8.4,2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.89 (d, J = 2.2 Hz, 1H),6.89-6.92 (m, 1H), 6.91 (d, J = 8.1 Hz, 1H), 6.95 (dd, J = 8.2, 2.2 Hz,1H), 7.35 (d, J = 8.2 Hz, 1H), 8.04 (d, J = 1.0 Hz, 1H), 8.48 (d, J =1.0 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 2.69(s, 3H), 3.47 (s, 3H), 3.84 (s, 3H), 4.88 (d, J = 13.6 Hz, 1H), 5.23 (d,J = 13.6 Hz, 1H), 6.09 (dd, J = 11.0, 2.4 Hz, 1H), 6.40 (td, J = 8.4,2.4 Hz, 1H), 6.74 (d, J = 7.9 Hz, 1H), 6.90 (d, J = 2.3 Hz, 1H),6.90-6.93 (m, 1H), 6.92 (d, J = 7.9 Hz, 1H), 6.96 (dd, J = 8.2, 2.3 Hz,1H), 7.37 (d, J = 8.2 Hz, 1H), 8.10 (d, J = 8.2 Hz, 2H), 8.32 (d, J =8.2 Hz, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 0.96 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 2.67(s, 1H), 2.71 (s, 3H), 3.47 (s, 3H), 3.85 (s, 3H), 4.89 (d, J = 13.5 Hz,1H), 5.23 (d, J = 13.5 Hz, 1H), 6.09 (d, J = 11.5, 2.4 Hz, 1H), 6.41(td, J = 8.3, 2.4 Hz, 1H), 6.74 (d, J = 7.9 Hz, 1H), 6.90 (d, J = 2.1Hz, 1H), 6.90- 6.93 (m, 1H), 6.93 (d, J = 7.9 Hz, 1H), 6.97 (dd, J =8.1, 2.1 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H),8.26 (d, J = 7.8 Hz, 1H), 8.43 (d, J = 7.8 Hz, 1H), 8.78 (s, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.95 (s, 3H), 1.28 (s, 3H), 2.03 (s, 3H), 2.73(s, 3H), 3.47 (s, 3H), 3.76 (s, 1H), 3.85 (s, 3H), 4.89 (d, J = 13.4 Hz,1H), 5.23 (d, J = 13.4 Hz, 1H), 6.09 (dd, J = 11.3, 2.4 Hz, 1H), 6.40(td, J = 8.3, 2.4 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H), 6.89 (d, J = 2.2Hz, 1H), 6.91 (d, J = 7.9 Hz, 1H), 6.66-6.92 (m, 1H), 6.95 (dd, J = 8.2,2.2 Hz, 1H), 7.28 (d, J = 5.2 Hz, 1H), 7.38 (d, J = 8.2 Hz, 1H), 8.66(d, J = 5.2 Hz, 1H), 9.35 (s, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.96 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.46(s, 3H), 3.73 (s, 1H), 3.83 (s, 3H), 4.86 (d, J = 13.7 Hz, 1H), 5.20 (d,J = 13.7 Hz, 1H), 6.07 (dd, J = 11.2, 2.4 Hz, 1H), 6.40 (td, J = 8.3,2.4 Hz, 1H), 6.57 (d, J = 3.7 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.87(d, J = 2.2 Hz, 1H), 6.88-6.92 (m, 1H), 6.90 (d, J = 8.1 Hz, 1H), 6.93(dd, J = 8.3, 2.2 Hz, 1H), 7.35 (d, J = 8.3 Hz, 1H), 7.36 (d, J = 3.7Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.95 (s, 3H), 1.28 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.83 (s, 3H), 4.86 (d, J = 13.5 Hz, 1H), 5.21 (d, J = 13.5 Hz,1H), 6.08 (dd, J = 11.2, 2.4 Hz, 1H), 6.40 (td, J = 8.3, 2.4 Hz, 1H),6.73 (d, J = 8.1 Hz, 1H), 6.87 (d, J = 2.2 Hz, 1H), 6.88-6.93 (m, 1H),6.90 (d, J = 8.1 Hz, 1H), 6.92 (dd, J = 8.2, 2.2 Hz, 1H), 7.04 (d, J =4.2 Hz, 1H), 7.35 (d, J = 8.2 Hz, 1H), 7.80 (d, J = 4.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.95 (s, 3H), 1.28 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.84 (s, 3H), 4.86 (d, J = 13.7 Hz, 1H), 5.22 (d, J = 13.7 Hz,1H), 6.08 (dd, J = 11.1, 2.4 Hz, 1H), 6.40 (td, J = 8.3, 2.4 Hz, 1H),6.73 (d, J = 8.1 Hz, 1H), 6.88- 6.92 (m, 3H), 6.96 (dd, J = 8.2, 2.2 Hz,1H), 7.12 (d, J = 5.3 Hz, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.61 (d, J =5.3 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.94 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 2.59(s, 3H), 3.47 (s, 3H), 3.72 (s, 1H), 3.83 (s, 3H), 4.87 (d, J = 13.6 Hz,1H), 5.22 (d, J = 13.6 Hz, 1H), 6.08 (dd, J = 11.2, 2.4 Hz, 1H), 6.39(td, J = 8.4, 2.4 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H), 6.86- 6.92 (m, 4H),6.93 (dd, J = 8.4, 2.6 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 7.82 (d, J =3.9 Hz, 1.1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.94 (s, 3H), 1.28 (s, 3H), 2.02 (s, 3H), 2.30(s, 3H), 3.47 (s, 3H), 3.73 (s, 1H), 3.84 (s, 3H), 4.87 (d, J = 13.7 Hz,1H), 5.22 (d, J = 13.7 Hz, 1H), 6.07 (dd, J = 11.0, 2.4 Hz, 1H), 6.40(td, J = 8.3, 2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.88-6.92 (m, 1H),6.90 (d, J = 8.1 Hz, 1H), 6.91 (d, J = 2.2 Hz, 1H), 6.95 (dd, J = 8.3,2,2 Hz, 1H), 7.33 (s, 1H), 7.35 (d, J = 8.3 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.97 (s, 3H), 1.28 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.75 (s, 1H), 3.84 (s, 3H), 4.86 (d, J = 13.6 Hz, 1H), 5.21 (d,J = 13.6 Hz, 1H), 6.08 (dd, J = 11.2, 2.4 Hz, 1H), 6.41 (td, J = 8.3,2.4 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.87 (d, J = 2.2 Hz, 1H),6.90-6.93 (m, 1H), 6.91 (d, J = 8.1 Hz, 1H), 6.94 (dd, J = 8.3, 2.2 Hz,1H), 7.38 (d, J = 8.3 Hz, 1H), 7.96 (dd, J = 5.1, 1.3 Hz, 1H), 8.08 (dd,J = 1.3, 0.7 Hz, 1H), 8.65 (dd, J = 5.1, 0.7 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.97 (s, 3H), 1.28 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.74 (s, 1H), 3.84 (s, 3H), 4.87 (d, J = 13.4 Hz, 1H), 5.22 (d,J = 13.4 Hz, 1H), 6.09 (dd, J = 11.3, 2.4 Hz, 1H), 6.41 (td, J = 8.4,2.4, 1H), 6.74 (d, J = 7.7 Hz, 1H), 6.88 (d, J = 2.1 Hz, 1H), 6.90-6.93(m, 1H), 6.91 (d, J = 7.7 Hz, 1H), 6.94 (dd, J = 8.2, 2.1 Hz, 1H), 7.38(d, J = 8.2 Hz, 1H), 7.52 (dd, J = 8.3, 0.6 Hz, 1H), 8.42 (dd, J = 8.3,2.4 Hz, 1H), 9.20 (dd, J = 2.4, 0.6 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.95 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.72 (s, 1H), 3.80 (s, 3H), 4.11 (s, 3H), 4.88 (d, J = 13.6 Hz,1H), 5.22 (d, J = 13.6 Hz, 1H), 5.22 (d, J = 13.6 Hz, 1H), 6.08 (dd, J =11.3, 2.4 Hz, 1H), 6.40 (td, J = 8.4, 2.4 Hz, 1H), 6.73 (d, J = 8.1 Hz,1H), 6.89- 6.92 (m, 1H), 6.90 (d, J = 2.1 Hz, 1H), 6.91 (d, J = 8.1 Hz,1H), 6.94 (dd, J = 8.2, 2.1 Hz, 1H), 7.04 (dd, J = 7.6, 5.0 Hz, 1H),7.36 (d, J = 8.2 Hz, 1H), 8.40 (dd, J = 7.6, 2.1 Hz, 1H), 8.41 (dd, J =5.0, 2.1 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.91 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 2.53(s, 3H), 3.48 (s, 3H), 3.71 (s, 1H), 3.89 (s, 3H), 4.88 (d, J = 13.8 Hz,1H), 5.25 (d, J = 13.8 Hz, 1H), 6.07 (dd, J = 11.2, 2.5 Hz, 1H), 6.39(td, J = 8.3, 2.5, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.88-6.91 (m, 1H),6.90 (d, J = 7.9 Hz, 1H), 7.05 (dd, J = 8.0, 2.1 Hz, 1H), 7.26-7.32 (m,1H), 7.30 (d, J = 8.0 Hz, 1H), 7.42 (dd, J = 8.0, 1.4 Hz, 1H), 7.46 (td,J = 7.3, 1.4 Hz, 1H), 7.76-7.78 (m, 2H), 8.45 (s, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 2.49(s, 3H), 3.46 (s, 3H), 3.74 (s, 1H), 3.77 (s, 3H), 5.13 (d, J = 13.4 Hz,1H), 5.31 (d, J = 13.4 Hz, 1H), 6.70 (d, J = 3.8 Hz, 1H), 6.77 (d, J =7.9 Hz, 1H), 6.84 (d, J = 2.2 Hz, 1H), 6.87 (dd, J = 8.1, 2.2 Hz, 1H),6.90 (d, J = 7.9 Hz, 1H), 7.23-7.27 (m, 1H), 7.32 (d, J = 8.1 Hz, 1H),7.35 (d, J = 7.9 Hz, 1H), 7.45 (d, J = 3.8 Hz, 1H), 8.33 (t, J = 7.9 Hz,1H), 8.26 (d, J = 7.9 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.77 (s, 3H), 3.96 (s, 1H), 3.99 (s, 3H), 5.14 (d, J = 12.8 Hz,1H), 5.31 (d, J = 12.8 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.78 (d, J =7.9 Hz, 1H), 6.84 (d, J = 2.1 Hz, 1H), 6.88 (dd, J = 8.3, 2.1 Hz, 1H),6.91 (d, J = 7.9 Hz, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.46 (d, J = 3.7 Hz,1H), 7.63 (t, J = 7.8 Hz, 1H), 8.33 (d, J = 7.8 Hz, 1H), 8.40 (d, J =7.8 Hz, 1H), 8.87 (s, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 2.46 (s, 3H), 2.47(s, 3H), 3.45 (s, 3H), 3.76 (s, 3H), 3.79 (s, 1H), 5.12 (d, J = 13.3 Hz,1H), 5.30 (d, J = 13.3 Hz, 1H), 6.46 (d, J = 1.6 Hz, 1H), 6.69 (d, J =3.7 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.82 (d, J = 2.2 Hz, 1H), 6.86(dd, J = 8.3, 2.2 Hz, 1H), 6.90 (d, J = 8.1 Hz, 1H), 7.31 (d, J = 8.3Hz, 1H), 7.44 (d, J = 3.7 Hz, 1H), 7.56 (d, J = 1.6 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.76 (s, 3H), 3.80 (s, 1H), 5.11 (d, J = 13.4 Hz, 1H), 5.30 (d,J = 13.4 Hz, 1H), 6.70 (d, J = 3.6 Hz, 1H), 6.77 (d, J = 8.1 Hz, 1H),6.86 (d, J = 1.8 Hz, 1H), 6.90 (dd, J = 8.1, 1.8 Hz, 1H), 6.90 (d, J =8.1 Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.45 (d, J = 3.6 Hz, 1H), 8.46(d, J = 2.0 Hz, 1H), 8.95 (d, J = 2.0 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.48 (s, 3H), 3.46(s, 3H), 3.77 (s, 3H), 3.81 (s, 1H), 5.15 (d, J = 13.2 Hz, 1H), 5.30 (d,J = 13.2 Hz, 1H), 6.71 (d, J = 3.8 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H),6.82 (d, J = 2.2 Hz, 1H), 6.87 (dd, J = 8.3, 2.2 Hz, 1H), 6.90 (d, J =7.9 Hz, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.45 (d, J = 3.8 Hz, 1H), 8.71(d, J = 0.6 Hz, 1H), 9.06 (d, J = 0.6 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 2.94(s, 3H), 3.46 (s, 3H), 3.77 (s, 3H), 3.80 (s, 1H), 5.14 (d, J = 13.4 Hz,1H), 5.30 (d, J = 13.4 Hz, 1H), 6.70 (d, J = 3.8 Hz, 1H), 6.77 (d, J =8.1 Hz, 1H), 6.81 (d, J = 2.1 Hz, 1H), 6.85 (dd, J = 8.3, 2.1 Hz, 1H),6.90 (d, J = 8.1 Hz, 1H), 7.31-7.33 (m, 1H), 7.34 (d, J = 8.3 Hz, 1H),7.45 (d, J = 3.8 Hz, 1H), 8.45 (dd, J = 1.9, 1.8 Hz, 1H), 8.71 (dd, J =4.9, 1.8 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.22 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 2.71(s, 3H), 3.47 (s, 3H), 3.78 (s, 3H), 5.14 (d, J = 13.1 Hz, 1H), 5.31 (d,J = 13.1 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.78 (d, J = 7.9 Hz, 1H),6.84 (d, J = 2.1 Hz, 1H), 6.88 (dd, J = 8.1, 2.1 Hz, 1H), 6.91 (d, J =7.9 Hz, 1H) 7.34 (d, J = 8.1 Hz, 1H), 7.46 (d, J = 3.7 Hz, 1H), 7.65 (t,J = 7.8 Hz, 1H), 8.25 (dt, J = 7.8, 1.6 Hz, 1H), 8.41 (dt, J = 7.8, 1.6Hz, 1H), 8.77 (t, J = 1.6 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.91 (s, 3H), 1.28 (s, 3H), 1.50 (s, 9H), 2.01(s, 3H), 3.46 (s, 3H), 3.70 (s, 1H), 3.84 (s, 3H), 3.95 (d, J = 6.1 Hz,2H), 4.83 (d, J = 13.8 Hz, 1H), 5.20 (br s, 1H), 5.21 (d, J = 13.8 Hz,1H), 6.04 (dd, J = 11.2, 2.4 Hz, 1H), 6.38 (td, J = 8.3, 2.4 Hz, 1H),6.71 (d, J = 8.1 Hz, 1H), 6.87 (d, J = 8.1 Hz, 1H), 6.87-6.91 (m, 1H),6.97 (dd, J = 7.5, 1.9 Hz, 1H), 7.25 (d, J = 7.5 Hz, 1H), 7.54 (d, J =1.9 Hz, 1H), 8.22 (br s, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.46(s, 3H), 3.77 (s, 3H), 3.78 (br s, 1H), 5.12 (d, J = 13.4 Hz, 1H), 5.30(d, J = 13.4 Hz, 1H), 6.70 (d, J = 3.9 Hz, 1H), 6.77 (d, J = 7.9 Hz,1H), 6.85 (dd, J = 9.2, 2.8 Hz, 1H), 6.88 (t, J = 2.8 Hz, 1H), 6.89 (d,J = 7.9 Hz, 1H), 7.11 (d, J = 5.2 Hz, 1H), 7.31 (d, J = 9.2 Hz, 1H),7.44 (d, J = 3.9 Hz, 1H), 7.60 (d, J = 5.2 Hz, 1H)

Example 168-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-[N-methyl-N-(pyridin-4-ylcarbonyl)amino]phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 16-1)

A mixture of8-(5-fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(pyridin-4-ylcarbonylamino)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 14-21, 13.9 mg, 0.0251 mmol), cessium carbonate (41.7 mg,0.128 mmol), and methyl iodide (4.7 μL, 0.075 mmol) was suspended inanhydrous N,N-dimethylformamide (0.5 ml) and stirred for 3 hours at roomtemperature. The mixture was diluted with ethyl acetate (10 mL). Themixture was washed with water (10 mL) and saturated brine (10 mL)successively, dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. The obtained residue waspurified by silica gel column chromatography (hexane-ethyl acetate) togive the titled compound (4.6 mg) as a yellow amorphous product. (Yield32%)

¹H-NMR (400 MHz, CDCl₃) δ 0.98 (s, 3H), 1.28 (s, 3H), 2.00 (s, 3H), 3.43(s, 3H), 3.55 (s, 3H), 3.61 (s, 3H), 3.76 (br s, 1H), 4.66 (d, J = 13.3Hz, 1H), 5.08 (d, J = 13.3 Hz, 1H), 6.00 (dd, J = 11.1, 2.4 Hz, 1H),6.44 (td, J = 8.4, 2.4 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.78 (d, J =8.2 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 6.92-6.95 (m, 1H), 7.19 (d, J =4.9 Hz, 2H), 7.20 (d, J = 8.2 Hz, 1H), 8.02 (s, 1H), 8.43 (d, J = 4.9Hz, 2H)Using any compounds among Compounds No. 14-17˜14-20 and availablecompounds, the following Compounds (No. 16-2˜16-5) were obtained by amethod similar to that of Compound No. 16-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 0.83 (s, 3H), 1.09 (s, 3 H), 1.90 (s, 3H),3.26 (s, 3H), 3.45 (s, 3H), 3.58 (s, 3H), 4.64 (d, J = 13.3 Hz, 1H),5.06 (d, J = 13.3 Hz, 1H), 6.03 (dd, J = 11.5, 2.4 Hz, 1H), 6.14 (s,1H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 1H), 6.78 (d,J = 8.1 Hz, 1H), 6.83 (dd, J = 7.8, 2.0 Hz, 1H), 6.87 (d, J = 2.0 Hz,1H), 7.01-7.04 (m, 1H), 7.10 (d, J = 7.8 Hz, 1H), 7.11 (t, J = 7.2 Hz,2H), 7.18 (t, J = 7.2 Hz, 1H), 7.28 (d, J = 7.2 Hz, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 1.01 (s, 3H), 1.29 (s, 3 H), 1.89 (s, 3H),2.01 (s, 3H), 3.31 (s, 3H), 3.48 (s, 3H), 3.78 (br s, 1H), 3.82 (s, 3H),4.80 (d, J = 13.2 Hz, 1H), 5.17 (d, J = 13.2 Hz, 1H), 6.06 (dd, J =11.1, 2.5 Hz, 1H), 6.40 (td, J = 8.3, 2.5 Hz, 1H), 6.75 (d, J = 8.1 Hz,1H), 6.77 (s, 1H), 6.86 (dd, J = 8.0, 1.8 Hz, 1H), 6.89 (d, J = 8.1 Hz,1H), 6.89-6.93 (m, 1H), 7.32 (d, J = 8.0 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.99 (s, 3H), 1.30 (s, 3 H), 2.00 (s, 3H),3.40 (s, 3H), 3.59 (s, 3H), 3.62 (s, 3H), 3.77 (br s, 1H), 4.62 (d, J =13.1 Hz, 1H), 5.05 (d, J = 13.1 Hz, 1H), 5.97 (d, J = 11.0 Hz, 1H), 6.45(t, J = 8.3 Hz, 1H), 6.62 (br s, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.79 (brs, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.93-6.96 (m, 1H), 7.11 (br s, 1H),7.15 (d, J = 7.8 Hz, 1H), 7.46 (br s, 1H), 7.54 (br s, 1H), 8.27 (br s,1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.01 (s, 3H), 1.30 (s, 3 H), 2.00 (s, 3H),3.40 (s, 3H), 3.57 (s, 3H), 3.61 (s, 3H), 3.76 (br s, 1H), 4.65 (d, J =13.1 Hz, 1H), 5.05 (d, J = 13.1 Hz, 1H), 6.01 (dd, J = 11.2, 2.4 Hz,1H), 6.45 (td, J = 8.3, 2.4 Hz, 1H), 6.57 (d, J = 1.9 Hz, 1H), 6.71 (d,J = 7.9 Hz, 1H), 6.78 (dd, J = 8.0, 1.9 Hz, 1H), 6.81 (d, J = 7.9 Hz,1H), 6.92-6.96 (m, 1H), 7.02 (dd, J = 7.8, 4.9 Hz, 1H), 7.20 (d, J = 8.0Hz, 1H), 7.59 (dt, J = 7.8, 1.9 Hz, 1H), 8.45 (dd, J = 4.9, 1.9 Hz, 1H),8.62 (d, J = 1.9 Hz, 1H)

Example 177-[4-(3-Chlorophenylaminocarbonyloxy)-2-methoxyphenyl]-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 17-1)

8-(5-Fluoro-2-methylphenoxymethyl)-7-(4-hydroxy-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 11, 20.3 mg, 0.0451 mmol) was dissolved in anhydrousdichloromethane (0.5 mL), then triethylamine (13.6 μL, 0.0977 mmol) and3-chlorophenyl isocyanate (6 μL, 0.05 mmol) were added to the mixturesuccessively. After the reaction mixture was stirred for 1 hour at roomtemperature, the mixture was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled compound (22.4mg) as a colorless solid. (Yield 82%)

¹H-NMR (500 MHz, CDCl₃) δ 0.94 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.72 (s, 1H), 3.83 (s, 3H), 4.87 (d, J = 13.7 Hz, 1H), 5.22 (d,J = 13.7 Hz, 1H), 6.07 (dd, J = 11.3, 2.4 Hz, 1H), 6.39 (td, J = 8.2,2.4 Hz, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.87 (d, J = 2.3 Hz, 1H), 6.89-6.92 (m, 1H), 6.89 (d, J = 7.9 Hz, 1H), 6.90 (dd, J = 8.2, 2.3 Hz, 1H),6.98 (br s, 1H), 7.11 (d, J = 7.6 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H),7.31-7.32 (m, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.59 (br s, 1H)Using any compounds among Compounds No. 8-2, 11, 13-2, and availablecompounds, the following Compounds (No. 17-2˜17-17) were obtained by amethod similar to that of Compound No. 17-1.

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.72 (s, 1H), 3.83 (s, 3H), 4.87 (d, J = 13.7 Hz, 1H), 5.22 (d,J = 13.7 Hz, 1H), 6.07 (dd, J = 11.2, 2.4 Hz, 1H), 6.39 (td, J = 8.3,2.4 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 6.88 (d, J = 2.3 Hz, 1H), 6.89(d, J = 8.0 Hz, 1H), 6.91 (dd, J = 8.2, 2.3 Hz, 1H), 7.00 (br s, 1H),7.12- 7.15 (m, 1H), 7.31-7.56 (m, 6H)

¹H-NMR (500 MHz, CDCl₃) δ 0.92 (s, 3H), 1.00 (t, J = 7.5 Hz, 3H), 1.26(s, 3H), 1.59-1.67 (m, 2H), 2.01 (s, 3H), 3.25-3.29 (m, 2H), 3.46 (s,3H), 3.71 (s, 1H), 3.81 (s, 3H), 4.86 (d, J = 13.7 Hz, 1H), 5.07 (t, J =6.1 Hz, 1H), 5.21 (d, J = 13.7 Hz, 1H) 6.05 (dd, J = 11.2, 2.3 Hz, 1H),6.38 (td, J = 8.3, 2.3 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.82 (d, J =2.2 Hz, 1H), 6.84 (dd, J = 8.0, 2.2 Hz, 1H), 6.87-6.91 (m, 1H), 6.88 (d,J = 8.1 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.91 (s, 3H), 1.26-1.27 (m, 6H), 1.26 (s, 3H),2.01 (s, 3H), 3.46 (s, 3H), 3.71 (s, 1H), 3.82 (s, 3H), 3.88-3.97 (m,1H), 4.86 (d, J = 13.7 Hz, 1H), 4.88- 4.90 (m, 1H), 5.22 (d, J = 13.7Hz, 1H), 6.05 (dd, J = 11.2, 2.4 Hz, 1H), 6.38 (td, J = 8.3, 2.4 Hz,1H), 6.71 (d, J = 8.1 Hz, 1H), 6.82 (d, J = 2.1 Hz, 1H), 6.84 (dd, J =8.3, 2.1 Hz, 1H), 6.87-6.91 (m, 1H), 6.88 (d, J = 8.1 Hz, 1H), 7.28 (d,J = 8.3 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.95 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.72 (s, 1H), 3.83 (s, 3H), 4.86 (d, J = 133 (s, 3H), 4.86 (d,J = 13.4 Hz, 1H), 5.21 (d, J = 13.4 Hz, 1H), 6.07 (dd, J = 11.3, 2.4 Hz,1H), 6.39 (td, J = 8.4, 2.4 Hz, 1H), 6.73 (d, J = 8.2 Hz, 1H), 6.87-6.93(m, 4H), 7.34 (d, J = 8.0 Hz, 1H), 7.42- 7.45 (m, 1H), 8.34 (br s, 1 H),8.39 (d, J = 3.9 Hz, 1 H), 8.79 (s, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.93 (s, 3H), 1.27 (s, 3H), 1.35-1.77 (m,10H), 2.01 (s, 3H), 3.46 (s, 3H), 3.58-3.60 (m, 1H), 3.81 (s, 3H), 4.86(d, J = 13.7 Hz, 1H), 4.94 (d, J = 8.2 Hz, 1H), 5.21 (d, J = 13.7 Hz,1H), 6.05 (dd, J = 11.0, 2.3 Hz, 1H), 6.38 (td, J = 8.3, 2.3 Hz, 1H),6.75 (d, J = 7.7 Hz, 1H), 6.83-6.90 (m, 4H), 7.26- 7.29 (m, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.92 (s, 3H), 1.27 (s, 3H), 2.01 (s, 3H), 3.46(s, 3H), 3.71 (s, 1H), 3.81 (s, 3H), 4.48 (d, J = 5.8 Hz, 2H), 4.86 (d,J = 13.7 Hz, 1H), 5.21 (d, J = 13.7 Hz, 1H), 5.39 (t, J = 5.8 Hz, 1H),6.05 (dd, J = 11.2, 2.4 Hz, 1H), 6.30- 6.32 (m, 1H), 6.36-6.40 (m, 2H),6.71 (d, J = 7.9 Hz, 1H), 6.82-6.90 (m, 4H), 7.28 (d, J = 8.0 Hz, 1H),7.41 (d, J = 1.2 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 0.94 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.71 (s, 1H), 3.83 (s, 3H), 3.94 (s, 3H), 4.88 (d, J = 13.6 Hz,1H), 5.22 (d, J = 13.6 Hz, 1H), 6.07 (dd, J = 11.3, 2.4 Hz, 1H), 6.39(td, J = 8.2, 2.4 Hz, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.88-6.93 (m, 3H),6.90 (d, J = 7.9 Hz, 1H), 6.92 (dd, J = 8.0, 2.3 Hz, 1H), 7.00 (t, J =7.8 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.62(br s, 1H), 8.12 (br s, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.27 (s, 3H), 2.02 (s, 3H), 2.34(s, 3H), 3.47 (s, 3H), 3.72 (s, 1H), 3.83 (s, 3H), 4.87 (d, J = 13.7 Hz,1H), 5.22 (d, J = 13.7 Hz, 1H), 6.07 (dd, J = 11.2, 2.4 Hz, 1H), 6.39(td, J = 8.3, 2.4 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H), 6.87-6.92 (m, 1H),6.88 (d, J = 2.2 Hz, 1H), 6.89 (d, J = 8.1 Hz, 1H), 6, 91 (dd, J = 8.1,2.2 Hz, 1H), 7.17 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.1 Hz, 1H), 7.36(d, J = 8.3 Hz, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.26 (s, 3H), 1.32 (t, J = 7.2Hz, 3H), 2.01 (s, 3H), 3.46 (s, 3H), 3.71 (s, 1H), 3.81 (s, 3H), 4.08(d, J = 5.3 Hz, 2H), 4.27 (q, J = 7.2 Hz, 2H), 4.86 (d, J = 13.4 Hz,1H), 5.21 (d, J = 13.4 Hz, 1H), 5.58 (t, J = 5.3 Hz, 1H), 6.05 (dd, J =11.2, 2.4 Hz, 1H), 6.38 (td, J = 8.3, 2.4 Hz, 1H), 6.71 (d, J = 8.0 Hz,1H), 6.82 (d, J = 2.3 Hz, 1H), 6.86 (dd, J = 8.1, 2.3 Hz, 1H), 6.87-6.91(m, 1H), 6.88 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.1 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.27 (s, 3H, 1.99 (s, 3H), 2.01(s, 3H), 3.46 (s, 3H), 3.63 (q, J = 5.6 Hz, 2H), 3.73 (q, J = 5.6 Hz,2H), 3.71 (s, 1H), 3.81 (s, 3H), 4.34 (t, J = 5.6 Hz, 2H), 4.86 (d, J =13.7 Hz, 1H), 5.21 (d, J = 13.7 Hz, 1H), 5.36 (t, J = 5.6 Hz, 1H), 5.64(s, 1H), 6.05 (dd, J = 11.4, 2.5 Hz, 1H), 6.18 (s, 1H), 6.38 (td, J =8.2, 2.5 Hz, 1H), 6.71 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 2.2 Hz, 1H),6.84 (dd, J = 8.2, 2.2 Hz, 1H), 6.87- 6.91 (m, 1H), 6.88 (d, J = 8.0 Hz,1H), 7.29 (d, J = 8.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.92 (s, 3H), 1.26 (s, 3H), 2.01 (s, 3H), 3.46(s, 3H), 3.70 (s, 1H), 3.82 (s, 3H), 4.49 (d, J = 5.9 Hz, 2H), 4.86 (d,J = 13.7 Hz, 1H), 5.21 (d, J = 13.7 Hz, 1H), 5.37 (t, J = 5.9 Hz, 1H),6.05 (dd, J = 11.2, 2.4 Hz, 1H), 6.38 (td, J = 8.3, 2.4 Hz, 1H), 6.71(d, J = 8.0 Hz, 1H), 6.84-6.91 (m, 3H), 6.88 (d, J = 8.0 Hz, 1H), 7.29(d, J = 8.3 Hz, 1H), 7.31- 7.39 (m, 5H)

¹H-NMR (400 MHz, CDCl₃) δ 0.90 (s, 3H), 1.28 (s, 3H), 2.00 (s, 3H), 3.45(s, 3H), 3.69 (s, 1H), 3.80 (s, 3H), 4.49 (d, J = 5.8 Hz, 2H), 4.83 (d,J = 13.7 Hz, 1H), 5.12 (t, J = 5.8 Hz, 1H), 5.21 (d, J = 13.7 Hz, 1H),6.03 (dd, J = 11.2, 2.4 Hz, 1H), 6.37 (td, J = 8.3, 2.4 Hz, 1H), 6.50(s, 1H), 6.70 (d, J = 8.1 Hz, 1H), 6.76 (dd, J = 8.2, 2.2 Hz, 1H), 6.86(d, J = 8.1 Hz, 1H), 6.86-6.90 (m, 1H), 7.20 (d, J = 8.2 Hz, 1H),7.28-7.35 (m, 5H), 7.33 (d, J = 2.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.91 (s, 3H), 1.29 (s, 3H), 2.02 (s, 3H), 3.47(s, 3H), 3.70 (s, 1H), 3.84 (s, 3H), 4.85 (d, J = 14.0 Hz, 1H), 5.22 (d,J = 14.0 Hz, 1H), 6.05 (dd, J = 11.2, 2.5 Hz, 1H), 6.38 (td, J = 8.2,2.5 Hz, 1H), 6.62 (s, 1H), 6.71 (d, J = 8.0 Hz, 1H), 6.72 (s, 1H), 6.82(dd, J = 8.2, 2.1 Hz, 1H), 6.87 (d, J = 8.0 Hz, 1H), 6.87-6.91 (m, 1H),7.14-7.19 (m, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.37- 7.40 (m, 4H), 7.39(d, J = 2.1 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.21 (s, 3H), 1.26 (d, J = 6.1 Hz, 6H), 1.41(s, 3H), 2.47 (s, 3H), 3.44 (s, 3H), 3.74 (s, 3H), 3.78 (s, 1H),3.89-3.93 (m, 1H), 4.87 (d, J = 8.0 Hz, 1H), 5.10 (d, J = 13.3 Hz, 1H),5.29 (d, J = 13.3 Hz, 1H), 6.69 (d, J = 3.9 Hz, 1H), 6.73-6.76 (m, 2H),6.75 (d, J = 8.1 Hz, 1H), 6.87 (d, J = 8.1 Hz, 1H), 7.23 (d, J = 7.6 Hz,1H), 7.43 (d, J = 3.9 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.21 (s, 3H), 1.42 (s, 3H), 2.47 (s, 3H), 3.45(s, 3H), 3.75 (s, 3H), 3.79 (s, 1H), 5.12 (d, J = 13.3 Hz, 1H), 5.29 (d,J = 13.3 Hz, 1H), 6.69 (d, J = 3.8 Hz, 1H), 6.76 (d, J = 7.9 Hz, 1H),6.80 (d, J = 2.1 Hz, 1H), 6.82 (dd, J = 7.9, 2.1 Hz, 1H), 6.88 (d, J =7.9 Hz, 1H), 6.97 (br s, 1H), 7.13 (t, J = 7.5 Hz, 1H), 7.28 (d, J = 7.9Hz, 1H), 7.36 (t, J = 7.5 Hz, 2H), 7.44 (d, J = 3.8 Hz, 1H), 7.47 (d, J= 7.5 Hz, 2H)

¹H-NMR (500 MHz, CDCl₃) δ 0.91 (s, 3H), 0.96 (t, J = 7.2 Hz, 3H), 1.29(s, 3H), 1.58 (sextet, J = 7.2 Hz, 2H), 2.01 (s, 3H), 3.26 (td, J = 7.2,5.7 Hz, 2H), 3.47 (s, 3H), 3.69 (s, 1H), 3.83 (s, 3H), 4.73 (t, J = 5.7Hz, 1H), 4.85 (d, J = 13.6 Hz, 1H), 5.22 (d, J = 13.6 Hz, 1H), 6.04 (dd,J = 11.3, 2.4 Hz 1H), 6.32 (s, 1H), 6.38 (td, J = 8.2, 2.4 Hz, 1H), 6.70(d, J = 8.1 Hz, 1H), 6.77 (dd, J = 8.1, 2.0 Hz, 1H), 6.87 (d, J = 8.1Hz, 1H), 6.88-6.90 (m, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.33 (d, J = 2.0Hz, 1H)

Example 188-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 18-1)

A mixture of8-(5-fluoro-2-methylphenoxymethyl)-7-(4-hydroxy-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 11, 153 mg, 0.340 mmol), 1,1′-carbonyldiimiazole (95.6 mg,0.590 mmol), and 4-dimethylaminopyridine (5.2 mg, 0.043 mmol) wasdissolved in anhydrous tetrahydrofuran (3 mL) and stirred for 1 hour atroom temperature. After morpholine (58.3 μL, 0.666 mmol) was added tothe reaction mixture and the mixture was stirred for 2 hour, the mixturewas purified by silica gel column chromatography (hexane-ethyl acetate)to give the titled compound (61.2 mg) as a colorless solid. (Yield 32%)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.27 (s, 3H), 2.01 (s, 3H), 3.46(s, 3H), 3.61 (br s, 2H), 3.72 (br s, 2H), 3.73 (br s, 1H), 3.75-3.79(m, 4H), 3.82 (s, 3H), 4.85 (d, J = 13.7 Hz, 1H), 5.21 (d, J = 13.7 Hz,1H), 6.06 (dd, J = 11.2, 2.4 Hz, 1H), 6.39 (td, J = 8.3, 2.4 Hz, 1H),6.71 (d, J = 8.0 Hz, 1H), 6.80 (d, J = 2.3 Hz, 1H), 6.83 (dd, J = 8.3,2.3 Hz, 1H), 6.88-6.92 (m, 1H), 6.89 (d, J = 8.0 Hz, 1H), 7.30 (d, J =8.3 Hz, 1H)Using any compounds among Compounds No. 11 and available compounds, thefollowing Compounds (No. 18-2 and 18-3) were obtained by a methodsimilar to that of Compound. No. 18-1.

¹H-NMR (400 MHz, CDCl₃) δ 0.92 (s, 3H), 1.27 (s, 3 H), 2.01 (s, 3H),3.05 (s, 3H), 3.14 (s, 3H), 3.46 (s, 3H), 3.71 (s, 1H), 3.81 (s, 3H),4.86 (d, J = 13.7 Hz, 1H), 5.21 (d, J = 13.7 Hz, 1H), 6.06 (dd, J =11.2, 2.4 Hz, 1H), 6.38 (td, J = 8.3, 2.4 Hz, 1H), 6.71 (d, J = 7.8 Hz,1H), 6.80 (d, J = 2.2 Hz, 1H), 6.83 (dd, J = 8.2, 2.2 Hz, 1H), 6.87-6.91(m, 1H), 6.88 (d, J = 7.8 Hz, 1H), 7.29 (d, J = 8.2 2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 0.93 (s, 3H), 1.27 (s, 3 H), 1.63-1.65 (m,2H), 1.97- 2.02 (m, 2H), 2.01 (s, 3H), 3.30 (br s, 1H), 3.40 (br s, 1H),3.46 (s, 3H), 3.70 (s, 1H), 3.82 (s, 3H), 3.96- 4.01 (m, 2H), 4.04 (brs, 1H), 4.86 (d, J = 13.7 Hz, 1H), 5.21 (d, J = 13.7 Hz, 1H), 6.06 (dd,J = 11.1, 2.4 Hz, 1H), 6.38 (td, J = 8.3, 2.4 Hz, 1H), 6.71 (d, J = 8.1Hz, 1H), 6.79 (d, J = 2.2 Hz, 1H), 6.83 (dd, J = 8.2, 2.2 Hz, 1H),6.88-6.91 (m, 1H), 6.89 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H)

Example 198-(5-Fluoro-2-methylphenoxymethyl)-7-[2-methoxy-4-(N-methyl-N-phenylaminocarbonyloxy)phenyl]-1,3,3trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 19)

A mixture8-(5-fluoro-2-methylphenoxymethyl)-7-(4-hydroxy-2-methoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 11, 25.4 mg, 0.0564 mmol) and N-methyl-N-phenylcarbamoylchloride (20.4 mg, 0.120 mmol) was dissolved in pyridine (1 mL), andstirred for 2 hours at 100° C. The reaction mixture was concentrated,and then the obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled compound (28.7mg) as a pale yellow amorphous product. (Yield 87%)

¹H-NMR (500 MHz, CDCl₃) δ 0.91 (s, 3H), 1.26 (s, 3H), 2.00 (s, 3H), 3.45(s, 3H), 3.46 (s, 3H), 3.70 (s, 1H), 3.80 (s, 3H), 4.83 (d, J = 13.6 Hz,1H), 5.19 (d, J = 13.6 Hz, 1H), 6.03 (d, J = 8.6 Hz, 1H), 6.37 (t, J =8.6 Hz, 1H), 6.70 (d, J = 7.9 Hz, 1H), 6.86- 6.90 (m, 3H), 6.87 (d, J =7.9 Hz, 1H), 7.27-7.30 (m, 2H), 7.38-7.47 (m, 4 H)

Example 207-(4-Aminoacetylamino-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-onehydrochloride (Compound No. 20)

7-(4-tert-Butoxycarbonylaminoacetylamino-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 15-31, 10.5 mg, 0.0173 mmol) was dissolved in 1,4-dioxane(0.2 mL), 4N 1,4-dioxane solution of hydrochloride (41.3 μL, 0.165 mmol)was added thereto. After the reaction mixture was stirred for 4 hours atroom temperature, it was diluted with hexane (10 mL). The precipitatedsolid was filtered to give the titled compound (7.8 mg) as a pale yellowsolid. (Yield 83%)

¹H-NMR (500 MHz, CDCl₃) δ 0.78 (s, 3H), 1.08 (s, 3H), 1.92 (s, 3H), 3.33(s, 3H), 3.78 (s, 3H), 3.80- 3.81 (m, 2H), 4.82 (d, J = 14.3 Hz, 1H),5.22 (d, J = 14.3 Hz, 1H), 6.10 (dd, J = 11.6, 2.4 Hz, 1H), 6.13 (s,1H), 6.49 (td, J = 8.4, 2.4 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 6.81 (d,J = 8.2 Hz, 1H), 6.98-7.01 (m, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.29 (dd,J = 8.2, 1.8 Hz, 1H), 7.43 (d, J = 1.8 Hz, 1H), 8.16 (br s, 2H), 8.20(br s, 1H), 10.66 (s, 1H)

Example 218-(2-Methoxyphenylaminomethyl)-7-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 21-1)

7-(4-Hydroxy-2-methoxyphenyl)-8-[N-(2-methoxyphenyl)-N-(9-fluorenylmethoxycarbonyl)aminomethyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 13-1, 30.0 mg, 0.0448 mmol) was dissolved in mixed solventof tetrahydrofuran (1 mL) and dichloromethane (1 mL), and triethylamine(25 μL, 0.18 mmol) and nicotynoyl chloride hydrochloride (12.0 mg,0.0674 mmol) were added successively. After the reaction mixture wasstirred for 40 minutes at room temperature, it was purified by silicagel column chromatography (hexane-ethyl acetate). The obtained colorlessamorphous product was dissolved in N,N-dimethylformamide (1 mL) andpiperidine (50 μL) was added thereto. After the reaction mixture wasstirred for 20 minutes at room temperature, it was diluted with ethylacetate (50 mL). The mixture was washed with water (50 mL) and saturatedbrine (50 mL) successively, dried over anhydrous magnesium sulfate, andthen the solvent was removed under reduced pressure. The obtainedresidue was purified by silica gel column chromatography (hexane-ethylacetate) to give the titled compound (13.0 mg) as a colorless solid.(Yield 52%)

¹H-NMR (400 MHz, CDCl₃) δ 1.19 (s, 3H), 1.43 (s, 3H), 3.47 (s, 3H), 3.74(s, 3H), 3.75 (s, 1H), 3.80 (s, 3H), 4.16 (d, J = 5.5 Hz, 2H), 4.50 (t,J = 5.5 Hz, 1H), 6.34 (dd, J = 7.8, 1.5 Hz, 1H), 6.57 (td, J = 7.8, 1.5Hz, 1H), 6.67 (dd, J = 7.8, 1.5 Hz, 1H), 6.71 (d, J = 7.9 Hz, 1H),6.71-6.75 (m, 1H), 6.82 (d, J = 2.2 Hz, 1H), 6.85 (d, J = 7.9 Hz, 1H),6.89 (dd, J = 8.2, 2.2 Hz, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.49 (ddd, J =8.0, 4.9, 0.8 Hz, 1H), 8.46 (dt, J = 8.0, 2.0 Hz, 1H), 8.87 (dd, J =4.9, 2.0 Hz, 1H), 9.41 (dd, J = 2.0, 0.8 Hz, 1 H)Using any compounds among Compounds No. 13-1, 13-3, and availablecompounds, the following Compounds (No. 21-2˜21-24) were obtained by amethod similar to that of Compound No. 14-1, 15-1, 17-1 or 18-1 followedby a method similar to that of Compound No. 21-1.

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.43 (s, 3 H), 3.47 (s, 3H),3.74 (s, 3H), 3.76 (s, 1H), 3.79 (s, 3H), 4.15 (s, 2H), 4.51 (br s, 1H),6.33 (dd, J = 7.8, 1.5 Hz, 1H), 6.56 (td, J = 7.8, 1.5 Hz, 1H), 6.61(dd, J = 3.6, 1.7 Hz, 1H), 6.66 (dd, J = 7.8, 1.5 Hz, 1H), 6.70 (d, J =8.1 Hz, 1H), 6.72 (td, J = 7.8, 1.5 Hz, 1H), 6.80 (d, J = 2.3 Hz, 1H),6.84 (d, J = 8.1 Hz, 1H), 6.87 (dd, J = 8.2, 2.3 Hz, 1H), 7.21 (d, J =8.2 Hz, 1H), 7.40 (dd, J = 3.6, 0.9 Hz, 1H), 7.69 (dd, J = 1.7, 0.9 Hz,1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.16 (s, 3H), 1.42 (s, 3 H), 3.46 (s, 3H),3.70 (s, 1H), 3.73 (s, 3H), 3.76 (s, 3H), 4.11 (s, 2H), 4.52 (br s, 1H),4.90 (s, 1H), 6.33 (dd, J = 7.7, 1.5 Hz, 1H), 6.43 (dd, J = 7.9, 2.3 Hz,1H), 6.44 (d, J = 2.3 Hz, 1H), 6.56 (td, J = 7.7, 1.5 Hz, 1H), 6.66 (dd,J = 7.7, 1.5 Hz, 1H), 6.68 (d, J = 8.1 Hz, 1H), 6.73 (td, J = 7.7, 1.5Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 7.9 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.43 (s, 3 H), 3.47 (s, 3H),3.74 (s, 3H), 3.80 (s, 3H), 4.16 (s, 2H), 4.50 (br s, 1H), 6.33 (d, J =7.8 Hz, 1H), 6.56 (t, J = 7.8 Hz, 1H), 6.66 (d, J = 7.8 Hz, 1H), 6.70(d, J = 7.9 Hz, 1H), 6.72 (t, J = 7.8 Hz, 1H), 6.83 (d, J = 2.2 Hz, 1H),6.84 (d, J = 7.9 Hz, 1H), 6.91 (dd, J = 8.2, 2.2 Hz, 1H), 7.23 (d, J =8.2 Hz, 1H), 7.39-7.43 (m, 1H), 7.49-7.55 (m, 2 H), 8.06 (dd, J = 8.1,1.2 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.06 (t, J = 7.4 Hz, 3H), 1.17 (s, 3H), 1.42(s, 3H), 1.75-1.85 (m, 2H), 2.55 (t, J = 7.4 Hz, 2H), 3.46 (s, 3H), 3.73(s, 4H), 3.77 (s, 3H), 4.13 (br s, 2H), 4.48 (br s, 1H), 6.31 (dd, J =7.9, 1.5 Hz, 1H), 6.56 (td, J = 7.9, 1.5 Hz, 1H), 6.65 (dd, J = 7.9, 1.5Hz, 1 H), 6.67 (d, J = 2.3 Hz, 1H), 6.69 (d, J = 7.9 Hz, 1H), 6.70-6.73(m, 1H), 6.74 (dd, J = 8.1, 2.3 Hz, 1H), 6.81 (d, J = 7.9 Hz, 1H), 7.16(d, J = 8.1 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.18 (s, 3H), 1.42 (s, 3 H), 3.47 (s, 3H),3.74 (s, 4H), 3.79 (s, 3H), 3.96 (s, 3H), 4.16 (br s, 2H), 4.51 (br s,1H), 6.33 (dd, J = 7.8, 1.4 Hz, 1H), 6.56 (td, J = 7.8, 1.4 Hz, 1H),6.66 (dd, J = 7.8, 1.4 Hz, 1H), 6.70 (d, J = 7.9 Hz, 1H), 6.72 (td, J =7.8, 1.4 Hz, 1H), 6.83 (d, J = 2.1 Hz, 1 H), 6.84 (d, J = 7.9 Hz, 1H),6.88 (dd, J = 8.1, 2.1 Hz, 1H), 7.05-7.08 (m, 1H), 7.05 (d, J = 7.6 Hz,1H), 7.21 (d, J = 8.1 Hz, 1H), 7.54- 7.58 (m, 1H), 8.03 (dd, J = 7.9,1.8 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.16 (s, 3H), 1.25 (d, J = 7.3 Hz, 6H), 1.41(s, 3H), 3.45 (s, 3H), 3.73 (s, 4 H), 3.77 (s, 3H), 3.88-3.95 (m, 1H),4.13 (br s, 2H), (m, 1H), 4.13 (br s, 2H), 4.51 (br s, 1H), 4.87 (d, J =7.6 Hz, 1H), 6.32 (dd, J = 7.8, 1.3 Hz, 1H), 6.55 (td, J = 7.8, 1.3 Hz,1H), 6.65 (dd, J = 7.8, 1.3 Hz, 1 H), 6.68 (d, J = 7.9 Hz, 1H),6.69-6.74 (m, 1H), 6.74 (d, J = 2.0 Hz, 1H), 6.77 (dd, J = 8.1, 2.0 Hz,1H), 6.80 (d, J = 7.9 Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.18 (s, 3H), 1.42 (s, 3 H), 3.47 (s, 3H),3.74 (s, 4H), 3.79 (s, 3H), 4.15 (br s, 2H), 4.50 (br s, 1H), 6.33 (dd,J = 7.8, 1.4 Hz, 1 H), 6.57 (td, J = 7.8, 1.4 Hz, 1H), 6.66 (dd, J =7.8, 1.4 Hz, 1H), 6.70 (d, J = 8.1 Hz, 1H), 6.71-6.74 (m, 1H), 6.82 (d,J = 2.1 Hz, 1 H), 6.84 (d, J = 8.1 Hz, 1H), 6.88 (dd, J = 8.2, 2.1 Hz,1H), 7.19 (dd, J = 5.0, 3.7 Hz, 1H), 7.21 (d, J = 8.2 Hz, 1H), 7.68 (dd,J = 5.0, 1.2 Hz, 1H), 7.99 (dd, J = 3.7, 1.2 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.16 (s, 3H), 1.42 (s, 3 H), 3.45 (s, 3H),3.59 (br s, 2H), 3.68 (br s, 2H), 3.73 (s, 3H), 3.75-3.77 (m, 5 H), 3.78(s, 3H), 4.12 (s, 2H), 4.52 (br s, 1H), 6.32 (dd, J = 7.7, 1.5 Hz, 1H),6.56 (td, J = 7.7, 1.5 Hz, 1H), 6.66 (dd, J = 7.7, 1.4 Hz, 1H), 6.69 (d,J = 7.9 Hz, 1H), 6.71 (d, J = 2.4 Hz, 1H), 6.72 (td, J = 7.7, 1.4 Hz,1H), 6.76 (dd, J = 8.2, 2.4 Hz, 1H), 6.82 (d, J = 7.9 Hz, 1H), 7.16 (d,J = 8.2 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.18 (s, 3H), 1.42 (s, 3 H), 3.47 (s, 3H),3.74 (s, 4H), 3.79 (s, 3H), 3.91 (s, 3H), 4.16 (d, J = 5.6 Hz, 2H), 4.51(t, J = 5.6 Hz, 1 H), 6.34 (dd, J = 7.7, 1.4 Hz, 1H), 6.57 (td, J = 7.7,1.4 Hz, 1H), 6.66 (dd, J = 7.7, 1.4 Hz, 1H), 6.70 (d, J = 7.9 Hz, 1H),6.73 (td, J = 7.7) 1.4 Hz, 1H), 6.80 (d, J = 2.1 Hz, 1H), 6.85 (d, J =7.9 Hz, 1H), 6.86 (dd, J = 8.1, 2.1 Hz, 1H), 7.00 (d, J = 8.9 Hz, 2H),7.21 (d, J = 8.1 Hz, 1H), 8.16 (d, J = 8.9 Hz, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.42 (s, 3 H), 3.47 (s, 3H),3.74 (s, 4H), 3.79 (s, 3H), 4.16 (s, 2H), 4.51 (br s, 1H), 6.33 (dd, J =7.8, 1.5 Hz, 1H), 6.57 (td, J = 7.8, 1.5 Hz, 1H), 6.66 (dd, J = 7.8, 1.5Hz, 1H), 6.70 (d, J = 8.1 Hz, 1H), 6.73 (td, J = 7.8, 1.5 Hz, 1H), 6.79,(d, J = 2.2 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 6.85 (dd, J = 8.2, 2.2Hz, 1H), 7.21 (d, J = 8.2 Hz, 1H), 7.40 (dd, J = 5.1, 3.0 Hz, 1H), 7.67(dd, J = 5.1, 1.2 Hz, 1H), 8.32 (dd, J = 3.0, 1.2 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.18 (s, 3H), 1.43 (s, 3H), 2.94 (s, 3H), 3.46(s, 3 H), 3.74 (s, 4H), 3.80 (s, 3H), 4.16-4.16 (m, 2H), 4.51 (br s,1H), 6.34 (dd, J = 7.9, 1.3 Hz, 1H), 6.57 (td, J = 7.9, 1.3 Hz, 1H),6.67 (dd, J = 7.9, 1.3 Hz, 1H), 6.71 (d, J = 7.9 Hz, 1H), 6.74 (td, J =7.9, 1.3 Hz, 1H), 6.79 (d, J = 2.2 Hz, 1H), 6.84 (d, J = 7.9 Hz, 1 H),6.86 (dd, J = 8.1, 2.2 Hz, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.31 (dd, J =7.8, 4.7 Hz, 1H), 8.44 (dd, J = 7.8, 1.8 Hz, 1H), 8.71 (dd, J = 4.7, 1.8Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.19 (s, 3H), 1.43 (s, 3H), 3.47 (s, 3H), 3.74(s, 3 H), 3.77 (s, 1H), 3.79 (s, 3H), 4.15 (br s, 2H), 4.49 (br s, 1H),6.32 (dd, J = 7.8, 1.4 Hz, 1H), 6.57 (td, J = 7.8, 1.4 Hz, 1H), 6.66(dd, J = 7.8, 1.4 Hz, 1H), 6.71 (d, J = 8.0 Hz, 1H), 6.72 (td, J = 7.8,1.4 Hz, 1 H), 6.84 (d, J = 8.0 Hz, 1H), 6.86 (d, J = 2.2 Hz, 1H), 6.92(dd, J = 8.2, 2.2 Hz, 1H), 7.23 (d, J = 8.2 Hz, 1H), 8.46 (d, J = 2.2Hz, 1H), 8.95 (d, J = 2.2 Hz, 1 H)

¹H-NMR (400 MHz, CDCl₃) δ 1.17 (s, 3H), 1.25-1.39 (m, 4H), 1.42 (s, 3H),1.58- 1.72 (m, 2H), 1.81-1.85 (m, 2H), 2.05-2.09 (m, 2H), 2.52-2.59 (m,1H), 3.45 (s, 3H), 3.73 (s, 4H), 3.77 (s, 3H), 4.14 (d, J = 3.4 Hz, 2H),4.48 (br s, 1H), 6.31 (dd, J = 7.8, 1.5 Hz, 1H), 6.55 (td, J = 7.8, 1.5Hz, 1H), 6.65 (dd, J = 7.8, 1.5 Hz, 1H), 6.65 (d, J = 2.2 Hz, 1H), 6.68(d, J = 7.9 Hz, 1H), 6.69-6.73 (m, 1H), 6.72 (dd, J = 8.1, 2.2 Hz, 1H),6.81 (d, J = 7.9 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1 H)

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.43 (s, 3 H), 2.70 (s, 3H),3.47 (s, 3H), 3.74 (s, 4H), 3.80 (s, 3H), 4.17 (d, J = 4.9 Hz, 2H), 4.52(t, J = 4.9 Hz, 1 H), 6.34 (dd, J = 7.8, 1.4 Hz, 1H), 6.57 (td, J = 7.8,1.4 Hz, 1H), 6.67 (dd, J = 7.8, 1.4 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H),6.73 (td, J = 7.8, 1.4 Hz, 1H), 6.79 (d, J = 2.1 Hz, 1H), 6.84 (d, J =8.0 Hz, 1H), 6.86 (dd, J = 8.1, 2.1 Hz, 1H), 7.23 (d, J = 8.1 Hz, 1H),7.33 (d, J = 7.3 Hz, 1H), 7.34- 7.36 (m, 1H), 7.48-7.52 (m, 1H),8.16-8.18 (m, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.17 (s, 3H), 1.41 (s, 3 H), 3.45 (s, 3H),3.71 (s, 3H), 3.72 (s, 1H), 3.74 (s, 3H), 3.87 (s, 2H), 4.10-4.13 (m,2H), 4.46 (br s, 1H), 6.30 (dd, J = 7.8, 1.6 Hz, 1H), 6.55 (td, J = 7.8,1.6 Hz, 1H), 6.63-6.73 (m, 2 H), 6.64 (dd, J = 7.8, 1.6 Hz, 1H), 6.68(d, J = 7.8 Hz, 1H), 6.71 (dd, J = 8.1, 2.2 Hz, 1H), 6.79 (d, J = 8.1Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.32-7.41 (m, 5H)

¹H-NMR (400 MHz, CDCl₃) δ 1.19 (s, 3H), 1.43 (s, 3 H), 3.47 (s, 3H),3.75 (s, 4H), 3.80 (s, 3H), 3.98 (s, 3.H), 4.16 (s, 2H), 4.51 (br s,1H), 6.34 (dd, J = 7.8, 1.5 Hz, 1H), 6.57 (td, J = 7.8, 1.5 Hz, 1H),6.67 (dd, J = 7.8, 1.5 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.74 (td, J =7.8, 1.5 Hz, 1H), 6.82 (d, J = 2.3 Hz, 1H), 6.85 (d, J = 8.1 Hz, 1H),6.89 (dd, J = 8.2, 2.3 Hz, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.63 (t, J =7.8 Hz, 1 H), 8.32 (dt, J = 7.8, 1.6 Hz, 1H), 8.39 (dt, J = 7.8, 1.6 Hz,1H), 8.86 (t, J = 1.6 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.42 (s, 3 H), 3.46 (s, 3H),3.74 (s, 4H), 3.79 (s, 3H), 4.15 (s, 2H), 4.50 (br s, 1H), 6.33 (dd, J =7.7, 1.5 Hz, 1H), 6.56 (td, J = 7.7, 1.5 Hz, 1H), 6.66 (dd, J = 7.7, 1.5Hz, 1H), 6.70 (d, J = 8.1 Hz, 1H), 6.73 (td, J = 7.7, 1.5 Hz, 1H), 6.77(d, J = 2.0 Hz, 1H), 6.83 (dd, J = 8.2, 2.0 Hz, 1H), 6.84 (d, J = 8.1Hz, 1H), 6.88 (dd, J = 1.8, 0.8 Hz, 1H), 7.21 (d, J = 8.2 Hz, 1H), 7.51(t, J = 1.8 Hz, 1H), 8.21 (dd, J = 1.8, 0.8 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.19 (s, 3H), 1.43 (s, 3H), 2.70 (s, 3H), 3.47(s, 3 H), 3.75 (s, 4H), 3.81 (s, 3H), 4.16-4.17 (m, 2H), 4.51 (br s,1H), 6.34 (dd, J = 7.8, 1.4 Hz, 1H), 6.57 (td, J = 7.8, 1.4 Hz, 1H),6.67 (dd, J = 7.8, 1.4 Hz, 1H), 6.71 (d, J = 8.0 Hz, 1H), 6.74 (td, J =7.8, 1.4 Hz, 1H), 6.82 (d, J = 2.1 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1 H),6.89 (dd, J = 8.2, 2.1 Hz, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.66 (t, J =7.8 Hz, 1H), 8.25 (dt, J = 7.8, 1.4 Hz, 1H), 8.41 (dt, J = 7.8, 1.4 Hz,1H), 8.77 (t, J = 1.4 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.43 (s, 3H), 3.46 (s, 3H), 3.74(s, 4 H), 3.80 (s, 3H), 4.15 (br s, 2H), 4.50 (br s, 1H), 6.33 (dd, J =7.8, 1.5 Hz, 1H), 6.56 (td, J = 7.8, 1.5 Hz, 1H), 6.66 (dd, J = 7.8, 1.5Hz, 1H), 6.70 (d, J = 7.8 Hz, 1H), 6.73 (td, J = 7.8, 1.5 Hz, 1H), 6.83(d, J = 7.8 Hz, 1H), 6.83 (d, J = 2.2 Hz, 1H), 6.88 (dd, J = 8.2, 2.2Hz, 1H), 7.11 (d, J = 5.2 Hz, 1H), 7.21 (d, J = 8.2 Hz, 1H), 7.60 (d, J= 5.2 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.18 (s, 3H), 1.42 (s, 3 H), 3.46 (s, 3H),3.72 (s, 3H), 3.73 (s, 1H), 3.77 (s, 3H), 3.92 (s, 3H), 4.14 (br s, 2H),4.46 (br s, 1H), 6.31 (dd, J = 7.7, 1.4 Hz, 1H), 6.56 (td, J = 7.7, 1.4Hz, 1H), 6.65 (dd, J = 7.7, 1.4 Hz, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.72(td, J = 7.7, 1.4 Hz, 1H), 6.76 (d, J = 2.3 Hz, 1H), 6.81 (d, J = 8.0Hz, 1H), 6.83 (dd, J = 8.1, 2.3 Hz, 1H), 7.18 (d, J = 8.1 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.40 (s, 3 H), 1.87 (s, 3H),2.70 (s, 3H), 3.43 (s, 3H), 3.77 (s, 1H), 3.80-3.85 (m, 1H), 3.81 (s,3H), 4.16-4.27 (m, 2 H), 6.03 (dd, J = 11.6, 2.5 Hz, 1H), 6.23 (td, J =8.3, 2.5 Hz, 1H), 6.72 (d, J = 7.9 Hz, 1H), 6.82-6.86 (m, 1H), 6.84 (d,J = 2.1 Hz, 1H), 6.87 (d, J = 7.9 Hz, 1 H), 6.90 (dd, J = 8.2, 2.1 Hz,1H), 7.26 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 7.3 Hz, 1H), 7.34 (t, J =7.3 Hz, 1H), 7.48-7.52 (m, 1H), 8.18 (d, J = 7.3 Hz, 1H)

¹H-NMR (400 MHz, CDCl₃) δ 1.18 (s, 3H), 1.42 (s, 3 H), 2.46 (s, 3H),3.46 (s, 3H), 3.73 (s, 4H), 3.79 (s, 3H), 4.15 (s, 2H), 4.49 (br s, 1H),6.32 (dd, J = 7.7, 1.4 Hz, 1H), 6.46 (d, J = 1.4 Hz, 1H), 6.56 (td, J =7.7, 1.4 Hz, 1H), 6.66 (dd, J = 7.7, 1.4 Hz, 1H), 6.70 (d, J = 8.0 Hz,1H), 6.72 (td, J = 7.7, 1.4 Hz, 1H), 6.81 (d, J = 2.2 Hz, 1H), 6.84 (d,J = 8.0 Hz, 1H), 6.87 (dd, J = 8.2, 2.2 Hz, 1 H), 7.21 (d, J = 8.2 Hz,1H), 7.55 (d, J = 1.4 Hz, 1H)

¹H-NMR (500 MHz, CDCl₃) δ 1.18 (s, 3H), 1.42 (s, 3 H), 3.46 (s, 3H),3.74 (s, 4H), 3.79 (s, 3H), 4.15 (s, 2H), 4.49 (br s, 1H), 6.33 (dd, J =7.7, 1.4 Hz, 1H), 6.57 (td, J = 7.7, 1.4 Hz, 1H), 6.66 (dd, J = 7.7, 1.4Hz, 1H), 6.70 (d, J = 7.9 Hz, 1H), 6.73 (td, J = 7.7, 1.4 Hz, 1H), 6.79(d, J = 2.1 Hz, 1H), 6.82 (d, J = 7.9 Hz, 1H), 6.84 (dd, J = 8.3, 2.1Hz, 1H), 7.03 (s, 1H), 7.20 (d, J = 8.3 Hz, 1 H), 7.31 (dd, J = 8.1, 4.7Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 8.38 (dd, J = 4.7, 2.1 Hz, 1H), 8.59(d, J = 2.1 Hz, 1H)

Example 227-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-8-(2-methoxy-5-nitrophenoxymethyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Compound No. 22)

A mixture of8-hydroxymethyl-7-[2-methoxy-4-(2-methylbenzoyloxy)phenyl]-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one(Reference Compound No. 23, 40.1 mg, 0.0898 mmol),2-methoxy-5-nitrophenol (22.8 mg, 0.135 mmol), and tri n-butylphosphine(33.7 μL, 0.135 mmol) was dissolved in anhydrous tetrahydrofuran (1 mL),1,1′-(azodicarbonyl)dipiperidine (34.0 mg, 0.135 mmol) was addedthereto, and then the mixture was stirred at room temperature. After 20minutes, 2-methoxy-5-nitrophenol (23.1 mg, 0.137 mmol), trin-butylphosphine (33.7 μL, 0.135 mmol), and1,1′-(azodicarbonyl)dipiperidine (33.9 mg, 0.134 mmol) were addedthereto, and after 80 minutes, 2-methoxy-5-nitrophenol (22.9 mg, 0.135mmol), tri-n-butylphosphine (33.7 μL, 0.135 mmol), and1,1′-(azodicarbonyl)dipiperidine (34.0 mg, 0.135 mmol) were addedfurther. The stir was stopped 3 hours later and the reaction mixture wasconcentrated. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled compound (22.1mg) as a pale yellow amorphous product. (Yield 41%)

¹H-NMR (500 MHz, CDCl₃) δ 1.43 (s, 3H), 1.43 (s, 3H), 2.71 (s, 3H), 3.78(s, 1H), 3.79 (s, 3H), 4.06 (s, 3H), 4.95 (d, J = 11.9 Hz, 1H), 5.13 (d,J = 11.9 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H),6.87 (d, J = 2.2 Hz, 1H), 6.94 (d, J = 9.1 Hz, 1H), 6.97 (dd, J = 8.2,2.2 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.35(t, J = 7.6 Hz, 1H), 7.51 (td, J = 7.6, 1.3 Hz, 1H), 7.56 (d, J = 2.5Hz, 1H), 7.94 (dd, J = 9.1, 2.5 Hz, 1H), 8.21 (dd, J = 7.6, 1.3 Hz, 1H),9.11 (s, 1H)

Preparation Examples

Hereinafter, typical preparation examples of the present compound areshown.

1) Tablet (in 150 mg) Present compound   1 mg Lactose 100 mg  Cornstarch 40 mg Carboxymethyl cellulose calcium 4.5 mg Hydroxypropyl cellulose  4 mg Magnesium stearate 0.5 mg

A tablet of the above-mentioned formulation is coated with 3 mg of acoating agent (for example, a conventional coating agent such ashydroxypropylmethyl cellulose, macrogol or a silicone resin), whereby anobjective tablet can be obtained. In addition, a desired tablet can beobtained by appropriately changing the kind and/or amount of the presentcompound and additives.

2) Capsule (in 150 mg) Present compound   5 mg Lactose 135 mg Carboxymethyl cellulose calcium 4.5 mg Hydroxypropyl cellulose   4 mgMagnesium stearate 1.5 mg

A desired capsule can be obtained by appropriately changing the kindand/or amount of the present compound and additives.

3) Eye drop (in 100 mL) Present compound 100 mg Sodium chloride 900 mgPolysorbate 80 500 mg Sodium hydroxide q.s. Hydrochloric acid q.s.Sterile purified water q.s.

A desired eye drop can be obtained by appropriately changing the kindand/or amount of the present compound and additives.

Pharmacological Test 1. Evaluation Test for Binding Activity toGlucocorticoid Receptor (Hereinafter Referred to as “GR”)

In order to evaluate a binding activity to GR, receptor competitor assaywas carried out by a fluorescence polarization method. In the assay, aGR competitor assay kit (manufactured by Invitrogen, cat No. P2816) wasused, and a procedure was carried out according to the protocol attachedto the kit. Hereinafter, the specific method will be described.

(Preparation of Reagents)

GR screening buffer: A buffer containing 10 mM potassium phosphate (pH7.4), 20 mM sodium molybdate (Na₂MoO₄), 0.1 mM ethylene diaminetetraacetic acid (EDTA), 5 mM dithiothreitol (DTT), 0.1 mM stabilizingpeptide and 2% dimethylsulfoxide was prepared.

4×GS1 solution: Fluormone™ GS1, which is a fluorescent glucocorticoidligand, was diluted with GR screening buffer, whereby a 4 nM solutionwas prepared.

4×GR solution: Recombinant human GR was diluted with GR screeningbuffer, whereby a 16 nM solution was prepared.

(Preparation of Test Compound Solution)

After a test compound was dissolved in dimethylsulfoxide, the resultingsolution was diluted with GR screening buffer, whereby a 20 μM testcompound solution was prepared.

(Test Method and Measurement Method)

1) The test compound solution was added in an amount of 25 μL into eachwell of a 96-well plate, and then, 4×GS1 solution and 4×GR solution wereadded in an amount of 12.5 μL into each well, respectively.

2) The plate was incubated in a dark place at room temperature for 2 to4 hours.

3) By using a multimode plate reader, Analyst™ HT (manufactured by LJLBiosystems), fluorescence polarization of each well was measured. As theblank, a well containing GR screening buffer in place of the testcompound and 4×GS1 solution was used.

4) The same procedure as that in the above 1) to 3) was carried outexcept that GR screening buffer was used in place of the test compoundsolution, and the obtained result was taken as the negative control.

5) The same procedure as that in the above 1) to 3) was carried outexcept that 2 mM dexamethasone was used in place of the test compoundsolution, and the obtained result was taken as the positive control.

(Calculation Equation of GR Binding Ratio)

A. GR binding ratio (%) was calculated from the following equation.

GR binding ratio(%)=100×[1−(fluorescence polarization of test compoundsolution−fluorescence polarization of positive controlsolution)/(fluorescence polarization of negative controlsolution−fluorescence polarization of positive control solution)]

(Test Results and Discussion)

As an example of the test results, the GR binding ratios (%) of the testcompounds (Compound 1-4, Compound 2-2, Compound 2-9, Compound 2-16,Compound 3-7, Compound 3-10, Compound 3-15, Compound 3-16, Compound3-17, Compound 4-5, Compound 4-7, Compound 4-10, Compound 4-11, Compound5-1, Compound 5-9, Compound 5-14, Compound 5-18, Compound 5-19, Compound5-21, Compound 5-22, Compound 5-24, Compound 6-4, Compound 6-8, Compound6-10, Compound 6-12, Compound 6-15, Compound 6-19, Compound 6-23,Compound 6-27, Compound 6-32, Compound 6-38, Compound 8-2, Compound 9-1,Compound 11, Compound 13-2, Compound 14-2, Compound 14-4, Compound14-11, Compound 14-21, Compound 14-22, Compound 14-30, Compound 14-33,Compound 14-35, Compound 14-36, Compound 14-37, Compound 14-44, Compound15-1, Compound 15-2, Compound 15-4, Compound 15-6, Compound 15-9,Compound 15-11, Compound 15-13, Compound 15-17, Compound 15-22, Compound15-24, Compound 16-3, Compound 17-5, Compound 17-16, Compound 18-1,Compound 18-2, Compound 21-3, Compound 21-5, Compound 21-12, Compound21-13, Compound 21-22, Compound 22) are shown in Table I.

TABLE I GR Binding ratio Test compound (%) Compound 1-4 91 Compound 2-299 Compound 2-9 99 Compound 2-16 100 Compound 3-7 100 Compound 3-10 100Compound 3-15 100 Compound 3-16 100 Compound 3-17 100 Compound 4-5 100Compound 4-7 100 Compound 4-10 100 Compound 4-11 100 Compound 5-1 100Compound 5-9 100 Compound 5-14 100 Compound 5-18 100 Compound 5-19 100Compound 5-21 100 Compound 5-22 99 Compound 5-24 100 Compound 6-4 98Compound 6-8 98 Compound 6-10 100 Compound 6-12 100 Compound 6-15 100Compound 6-19 100 Compound 6-23 98 Compound 6-27 100 Compound 6-32 89Compound 6-38 100 Compound 8-2 100 Compound 9-1 100 Compound 11 100Compound 13-2 91 Compound 14-2 100 Compound 14-4 100 Compound 14-11 100Compound 14-21 100 Compound 14-22 100 Compound 14-30 100 Compound 14-33100 Compound 14-35 93 Compound 14-36 88 Compound 14-37 93 Compound 14-44100 Compound 15-1 100 Compound 15-2 100 Compound 15-4 98 Compound 15-6100 Compound 15-9 100 Compound 15-11 100 Compound 15-13 100 Compound15-17 95 Compound 15-22 100 Compound 15-24 94 Compound 16-3 86 Compound17-5 91 Compound 17-16 88 Compound 18-1 100 Compound 18-2 99 Compound21-3 100 Compound 21-5 98 Compound 21-12 100 Compound 21-13 94 Compound21-22 100 Compound 22 100

As is apparent from Table I, the present compound showed an excellent GRbinding activity. Accordingly, the present compound can be used as a GRmodulator, and is useful for a preventive or therapeutic agentparticularly for GR-related diseases, that is, metabolic disorders,inflammatory diseases, autoimmune diseases, allergic diseases, centralnervous system diseases, cardiovascular diseases, homeostasis-relateddiseases, glaucoma and the like.

INDUSTRIAL APPLICABILITY

1,2,3,4-tetrahydroquinoxaline derivative or the salt according to thepresent invention has a binding activity to GR and is useful for GRmodulator of nonsteroidal compound.

1. A compound represented by the following formula (1) or a saltthereof:

wherein R¹ represents a halogen atom, a lower alkyl group which may haveat least a substituent, a lower cycloalkyl group which may have at leasta substituent, an aryl group which may have at least a substituent, aheterocyclic group which may have at least a substituent, a hydroxygroup, an ester of a hydroxy group, a lower alkoxy group which may haveat least a substituent, a lower cycloalkyloxy group which may have atleast a substituent, an aryloxy group which may have at least asubstituent, a heterocyclic oxy group which may have at least asubstituent, a mercapto group, an ester of a mercapto group, a loweralkylthio group which may have at least a substituent, a lowercycloalkylthio group which may have at least a substituent, an arylthiogroup which may have at least a substituent, a heterocyclic thio groupwhich may have at least a substituent, an amino group, a loweralkylamino group which may have at least a substituent, a lowercycloalkylamino group which may have at least a substituent, anarylamino group which may have at least a substituent, a heterocyclicamino group which may have at least a substituent, an amide of an aminogroup, an amide of a lower alkylamino group which may have at least asubstituent, an amide of a lower cycloalkylamino group which may have atleast a substituent, an amide of an arylamino group which may have atleast a substituent, an amide of a heterocyclic amino group which mayhave at least a substituent, a formyl group, a lower alkylcarbonyl groupwhich may have at least a substituent, a lower cycloalkylcarbonyl groupwhich may have at least a substituent, an arylcarbonyl group which mayhave at least a substituent, a heterocyclic carbonyl group which mayhave at least a substituent, a carboxy group, an ester of a carboxygroup, an amide of a carboxy group, a lower alkylsulfonyl group whichmay have at least a substituent, a lower cycloalkylsulfonyl group whichmay have at least a substituent, an arylsulfonyl group which may have atleast a substituent, a heterocyclic sulfonyl group which may have atleast a substituent, a sulfonic acid group, an ester of a sulfonic acidgroup, an amide of a sulfonic acid group, a nitro group or a cyanogroup; p represents an integer of 0 to 5; in the case where p is 2 to 5,each R¹ may be the same or different; R² represents a halogen atom, alower alkyl group which may have at least a substituent, a hydroxygroup, an ester of a hydroxy group or a lower alkoxy group which mayhave at least a substituent; q represents an integer of 0 to 2; in thecase where q is 2, each R² may be the same or different; R³ represents ahydrogen atom, a lower alkyl group which may have at least asubstituent, a lower alkenyl group which may have at least asubstituent, a lower alkylcarbonyl group which may have at least asubstituent, a lower alkenylcarbonyl group which may have at least asubstituent or an arylcarbonyl group which may have at least asubstituent; R⁴ and R⁵ are the same or different and represent a halogenatom, a lower alkyl group which may have at least a substituent, a loweralkenyl group which may have at least a substituent, a lower alkynylgroup which may have at least a substituent, a lower cycloalkyl groupwhich may have at least a substituent, an aryl group which may have atleast a substituent or a heterocyclic group which may have at least asubstituent; R⁴ and R⁵ may be combined together to form a 3- to8-membered lower cycloalkane ring which may have at least a substituent;R⁶ represents a hydrogen atom, a lower alkyl group which may have atleast a substituent, a lower alkenyl group which may have at least asubstituent, a lower alkynyl group which may have at least asubstituent, a lower cycloalkyl group which may have at least asubstituent, an aryl group which may have at least a substituent or aheterocyclic group which may have at least a substituent; A represents alower alkylene group which may have at least a substituent; R⁷represents OR⁸, NR⁸R⁹, SR⁸, S(O)R⁸ or S(O)₂R⁸; R⁸ and R⁹ are the same ordifferent and represent a hydrogen atom, a lower alkyl group which mayhave at least a substituent, a lower alkenyl group which may have atleast a substituent, a lower alkynyl group which may have at least asubstituent, a lower cycloalkyl group which may have at least asubstituent, an aryl group which may have at least a substituent, aheterocyclic group which may have at least a substituent, a formylgroup, a lower alkylcarbonyl group which may have at least asubstituent, a lower alkenylcarbonyl group which may have at least asubstituent, a lower alkynylcarbonyl group which may have at least asubstituent, a lower cycloalkylcarbonyl group which may have at least asubstituent, an arylcarbonyl group which may have at least asubstituent, a heterocyclic carbonyl group which may have at least asubstituent, a carboxy group, a lower alkoxycarbonyl group which mayhave at least a substituent, a lower alkenyloxycarbonyl group which mayhave at least a substituent, a lower alkynyloxycarbonyl group which mayhave at least a substituent, a lower cycloalkyloxycarbonyl group whichmay have at least a substituent, an aryloxycarbonyl group which may haveat least a substituent, a heterocyclic oxycarbonyl group which may haveat least a substituent, a lower alkylsulfonyl group which may have atleast a substituent, a lower alkenylsulfonyl group which may have atleast a substituent, a lower alkynylsulfonyl group which may have atleast a substituent, a lower cycloalkylsulfonyl group which may have atleast a substituent, an arylsulfonyl group which may have at least asubstituent, a heterocyclic sulfonyl group which may have at least asubstituent, an aminocarbonyl group, a lower alkylaminocarbonyl groupwhich may have at least a substituent, a lower alkenylaminocarbonylgroup which may have at least a substituent, a loweralkynylaminocarbonyl group which may have at least a substituent, alower cycloalkylaminocarbonyl group which may have at least asubstituent, an arylaminocarbonyl group which may have at least asubstituent or a heterocyclic aminocarbonyl group which may have atleast a substituent; in the case where R⁷ is NR⁸R⁹, R⁸ and R⁹ may becombined together to form a 3- to 8-membered nitrogen-containingheterocyclic ring which may have at least a substituent; and Xrepresents O or S.
 2. The compound or a salt thereof according to claim1, wherein in the formula (1), R¹ represents a halogen atom, a loweralkyl group, a lower cycloalkyl group, an aryl group, a heterocyclicgroup, a hydroxy group, an ester of a hydroxy group, a lower alkoxygroup, a lower cycloalkyloxy group, an aryloxy group, a heterocyclic oxygroup, a mercapto group, an ester of a mercapto group, a lower alkylthiogroup, a lower cycloalkylthio group, an arylthio group, a heterocyclicthio group, an amino group, a lower alkylamino group, a lowercycloalkylamino group, an arylamino group, a heterocyclic amino group,an amide of an amino group, an amide of a lower alkylamino group, anamide of a lower cycloalkylamino group, an amide of an arylamino group,an amide of a heterocyclic amino group, a lower alkylcarbonyl group, alower cycloalkylcarbonyl group, an arylcarbonyl group, a heterocycliccarbonyl group, a carboxy group, an ester of a carboxy group, an amideof a carboxy group, a lower alkylsulfonyl group, a lowercycloalkylsulfonyl group, an arylsulfonyl group, a heterocyclic sulfonylgroup, a sulfonic acid group, an ester of a sulfonic acid group, anamide of a sulfonic acid group, a nitro group or a cyano group; in thecase where R¹ is a lower alkyl group, a lower alkoxy group, a loweralkylthio group, a lower alkylamino group, an amide of a loweralkylamino group, a lower alkylcarbonyl group or a lower alkylsulfonylgroup, the lower alkyl group, lower alkoxy group, lower alkylthio group,lower alkylamino group, amide of a lower alkylamino group, loweralkylcarbonyl group or lower alkylsulfonyl group may have one or aplurality of groups selected from a halogen atom, a lower cycloalkylgroup, an aryl group, a heterocyclic group, a hydroxy group, an ester ofa hydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith at least a halogen atom, a lower cycloalkyloxy group, an aryloxygroup, a heterocyclic oxy group, a lower alkylthio group, a lowercycloalkylthio group, an arylthio group, a heterocyclic thio group, anamino group, a lower alkylamino group, a lower cycloalkylamino group, anarylamino group, a heterocyclic amino group, an amide of an amino group,an amide of a lower alkylamino group, an amide of a lowercycloalkylamino group, an amide of an arylamino group, an amide of aheterocyclic amino group, a lower alkylcarbonyl group, a lowercycloalkylcarbonyl group, an arylcarbonyl group, a heterocyclic carbonylgroup, a carboxy group, an ester of a carboxy group, an amide of acarboxy group, a lower alkylsulfonyl group, a lower cycloalkylsulfonylgroup, an arylsulfonyl group, a heterocyclic sulfonyl group, a sulfonicacid group, an ester of a sulfonic acid group, an amide of a sulfonicacid group, a nitro group and a cyano group as substituents; in the casewhere R¹ is a lower cycloalkyl group, an aryl group, a heterocyclicgroup, a lower cycloalkyloxy group, an aryloxy group, a heterocyclic oxygroup, a lower cycloalkylthio group, an arylthio group, a heterocyclicthio group, a lower cycloalkylamino group, an arylamino group, aheterocyclic amino group, an amide of a lower cycloalkylamino group, anamide of an arylamino group, an amide of a heterocyclic amino group, alower cycloalkylcarbonyl group, an arylcarbonyl group, a heterocycliccarbonyl group, a lower cycloalkylsulfonyl group, an arylsulfonyl groupor a heterocyclic sulfonyl group, the lower cycloalkyl group, arylgroup, heterocyclic group, lower cycloalkyloxy group, aryloxy group,heterocyclic oxy group, lower cycloalkylthio group, arylthio group,heterocyclic thio group, lower cycloalkylamino group, arylamino group,heterocyclic amino group, amide of a lower cycloalkylamino group, amideof an arylamino group, amide of a heterocyclic amino group, lowercycloalkylcarbonyl group, arylcarbonyl group, heterocyclic carbonylgroup, lower cycloalkylsulfonyl group, arylsulfonyl group orheterocyclic sulfonyl group may have one or a plurality of groupsselected from a halogen atom, a lower alkyl group, a lower alkyl groupsubstituted with at least a halogen atom, a hydroxy group, an ester of ahydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith at least a halogen atom, a lower alkylthio group, an amino group, alower alkylamino group, an amide of an amino group, an amide of a loweralkylamino group, a lower alkylcarbonyl group, a carboxy group, an esterof a carboxy group, an amide of a carboxy group, a lower alkylsulfonylgroup, a sulfonic acid group, an ester of a sulfonic acid group, anamide of a sulfonic acid group, a nitro group and a cyano group assubstituents; p represents an integer of 0 to 3; in the case where p is2 or 3, each R¹ may be the same or different; R² represents a halogenatom, a lower alkyl group, a hydroxy group or a lower alkoxy group; qrepresents an integer of 0 to 2; in the case where q is 2, each R² maybe the same or different; R³ represents a hydrogen atom, a lower alkylgroup, a lower alkenyl group, a lower alkylcarbonyl group, a loweralkenylcarbonyl group or an arylcarbonyl group; in the case where R³ isa lower alkyl group or a lower alkylcarbonyl group, the lower alkylgroup or lower alkylcarbonyl group may have one or a plurality ofsubstituents selected from the group consisting of a halogen atom and anaryl group; in the case where R³ is an arylcarbonyl group, thearylcarbonyl group may have one or a plurality of substituents selectedfrom the group consisting of a halogen atom, a lower alkyl group, alower alkyl group substituted with at least a halogen atom, a loweralkoxy group and a lower alkoxy group substituted with at least ahalogen atom; R⁴ and R⁵ are the same or different and represent ahalogen atom, a lower alkyl group, a lower cycloalkyl group, aryl or aheterocyclic group; in the case where R⁴ or R⁵ is a lower alkyl group,the lower alkyl group may have one or a plurality of substituentsselected from the group consisting of a halogen atom, a lower cycloalkylgroup, an aryl group, a heterocyclic group, a hydroxy group, an ester ofa hydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith at least a halogen atom, a lower cycloalkyloxy group, an aryloxygroup, a heterocyclic oxy group, a lower alkylthio group, a lowercycloalkylthio group, an arylthio group, a heterocyclic thio group, anamino group, a lower alkylamino group, a lower cycloalkylamino group, anarylamino group, a heterocyclic amino group, an amide of an amino group,an amide of a lower alkylamino group, an amide of a lowercycloalkylamino group, an amide of an arylamino group, an amide of aheterocyclic amino group, a lower alkylcarbonyl group, a lowercycloalkylcarbonyl group, an arylcarbonyl group, a heterocyclic carbonylgroup, a carboxy group, an ester of a carboxy group, an amide of acarboxy group, a nitro group and a cyano group; in the case where R⁴ orR⁵ is a lower cycloalkyl group, aryl or a heterocyclic group, the lowercycloalkyl group, aryl or heterocyclic group may have one or a pluralityof substituents selected from the group consisting of a halogen atom, alower alkyl group, a lower alkyl group substituted with at least ahalogen atom, a hydroxy group, an ester of a hydroxy group, a loweralkoxy group, a lower alkoxy group substituted with at least a halogenatom, a lower alkylthio group, an amino group, a lower alkylamino group,an amide of an amino group, an amide of a lower alkylamino group, alower alkylcarbonyl group, a carboxy group, an ester of a carboxy group,an amide of a carboxy group, a lower alkylsulfonyl group, a sulfonicacid group, an ester of a sulfonic acid group, an amide of a sulfonicacid group, a nitro group and a cyano group; R⁴ and R⁵ may be combinedtogether to form a 3- to 8-membered lower cycloalkane ring; R⁶represents a hydrogen atom, a lower alkyl group, a lower alkenyl group,a lower alkynyl group or a lower cycloalkyl group; in the case where R⁶is a lower alkyl group, a lower alkenyl group, a lower alkynyl group ora lower cycloalkyl group, the lower alkyl group, lower alkenyl group,lower alkynyl group or lower cycloalkyl group may have one or aplurality of substituents selected from the group consisting of ahalogen atom and an aryl group as substituents; A represents a loweralkylene group which may be substituted with at least a hydroxy group ora halogen atom; R⁷ represents OR⁸, NR⁸R⁹ or SR⁸; R⁸ and R⁹ may be thesame or different and represent a hydrogen atom, a lower alkyl group, alower alkenyl group, a lower alkynyl group, a lower cycloalkyl group, anaryl group, a heterocyclic group, a formyl group, a lower alkylcarbonylgroup, a lower alkenylcarbonyl group, a lower alkynylcarbonyl group, alower cycloalkylcarbonyl group, an arylcarbonyl group, a heterocycliccarbonyl group, a carboxy group, a lower alkoxycarbonyl group, a loweralkenyloxycarbonyl group, a lower alkynyloxycarbonyl group, a lowercycloalkyloxycarbonyl group, an aryloxycarbonyl group, a heterocyclicoxycarbonyl group, a lower alkylsulfonyl group, a lower alkenylsulfonylgroup, a lower alkynylsulfonyl group, a lower cycloalkylsulfonyl group,an arylsulfonyl group, a heterocyclic sulfonyl group, an aminocarbonylgroup, a lower alkylaminocarbonyl group, a lower alkenylaminocarbonylgroup, a lower alkynylaminocarbonyl group, a lowercycloalkylaminocarbonyl group, an arylaminocarbonyl group or aheterocyclic aminocarbonyl group; in the case where R⁸ or R⁹ is a loweralkyl group, a lower alkenyl group, a lower alkynyl group, a loweralkylcarbonyl group, a lower alkenylcarbonyl group, a loweralkynylcarbonyl group, a lower alkoxycarbonyl group, a loweralkenyloxycarbonyl group, a lower alkynyloxycarbonyl group, a loweralkylsulfonyl group, a lower alkenylsulfonyl group, a loweralkynylsulfonyl group, a lower alkylaminocarbonyl group, a loweralkenylaminocarbonyl group or a lower alkynylaminocarbonyl group, thelower alkyl group, lower alkenyl group, lower alkynyl group, loweralkylcarbonyl group, lower alkenylcarbonyl group, lower alkynylcarbonylgroup, lower alkoxycarbonyl group, lower alkenyloxycarbonyl group, loweralkynyloxycarbonyl group, lower alkylsulfonyl group, loweralkenylsulfonyl group, lower alkynylsulfonyl group, loweralkylaminocarbonyl group, lower alkenylaminocarbonyl group or loweralkynylaminocarbonyl group may have one or a plurality of substituentsselected from the group consisting of a halogen atom, a lower cycloalkylgroup, an aryl group, a heterocyclic group, a hydroxy group, an ester ofa hydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith at least a halogen atom, a lower cycloalkyloxy group, an aryloxygroup, a heterocyclic oxy group, a lower alkylthio group, a lowercycloalkylthio group, an arylthio group, a heterocyclic thio group, anamino group, a lower alkylamino group, a lower cycloalkylamino group, anarylamino group, a heterocyclic amino group, an amide of an amino group,an amide of a lower alkylamino group, an amide of a lowercycloalkylamino group, an amide of an arylamino group, an amide of aheterocyclic amino group, a lower alkylcarbonyl group, a lowercycloalkylcarbonyl group, an arylcarbonyl group, a heterocyclic carbonylgroup, a carboxy group, an ester of a carboxy group, an amide of acarboxy group, a lower alkylsulfonyl group, a lower cycloalkylsulfonylgroup, an arylsulfonyl group, a heterocyclic sulfonyl group, a sulfonicacid group, an ester of a sulfonic acid group, an amide of a sulfonicacid group, a nitro group and a cyano group; in the case where R⁸ or R⁹is a lower cycloalkyl group, an aryl group, a heterocyclic group, alower cycloalkylcarbonyl group, an arylcarbonyl group, a heterocycliccarbonyl group, a lower cycloalkyloxycarbonyl group, an aryloxycarbonylgroup, a heterocyclic oxycarbonyl group, a lower cycloalkylsulfonylgroup, an arylsulfonyl group, a heterocyclic sulfonyl group, a lowercycloalkylaminocarbonyl group, an arylaminocarbonyl group or aheterocyclic aminocarbonyl group, the lower cycloalkyl group, arylgroup, heterocyclic group, lower cycloalkylcarbonyl group, arylcarbonylgroup, heterocyclic carbonyl group, lower cycloalkyloxycarbonyl group,aryloxycarbonyl group, heterocyclic oxycarbonyl group, lowercycloalkylsulfonyl group, arylsulfonyl group, heterocyclic sulfonylgroup, lower cycloalkylaminocarbonyl group, arylaminocarbonyl group orheterocyclic aminocarbonyl group may have one or a plurality ofsubstituents selected from the group consisting of a halogen atom, alower alkyl group, a lower alkyl group substituted with at least ahalogen atom, a lower alkyl group substituted with at least a hydroxygroup, a lower alkenyl group, a lower alkynyl group, a lower cycloalkylgroup, an aryl group, a heterocyclic group, a hydroxy group, an ester ofa hydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith at least a halogen atom, a lower alkenyloxy group, a loweralkynyloxy group, a lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a lower alkylthio group, a lower cycloalkylthiogroup, an arylthio group, a heterocyclic thio group, an amino group, alower alkylamino group, a lower cycloalkylamino group, an arylaminogroup, a heterocyclic amino group, an amide of an amino group, an amideof a lower alkylamino group, an amide of a lower cycloalkylamino group,an amide of an arylamino group, an amide of a heterocyclic amino group,a lower alkylcarbonyl group, a lower cycloalkylcarbonyl group, anarylcarbonyl group, a heterocyclic carbonyl group, a carboxy group, anester of a carboxy group, an amide of a carboxy group, a loweralkylsulfonyl group, a lower cycloalkylsulfonyl group, an arylsulfonylgroup, a heterocyclic sulfonyl group, a sulfonic acid group, an ester ofa sulfonic acid group, an amide of a sulfonic acid group, a nitro groupand a cyano group; in the case where R⁷ is NR⁸R⁹, R⁸ and R⁹ may becombined together to form a 5- or 6-membered nitrogen-containingheterocyclic ring; and X represents O or S.
 3. The compound or a saltthereof according to claim 1, wherein in the formula (1), R¹ representsa halogen atom, a lower alkyl group, a hydroxy group, an ester of ahydroxy group, a lower alkoxy group, a lower alkylthio group, an aminogroup, a lower alkylamino group, an amide of an amino group, an amide ofa lower alkylamino group, a lower alkylcarbonyl group, a carboxy group,an ester of a carboxy group, an amide of a carboxy group, a loweralkylsulfonyl group, a nitro group or a cyano group; in the case whereR¹ is a lower alkyl group, a lower alkoxy group, a lower alkylthiogroup, a lower alkylamino group, an amide of a lower alkylamino group, alower alkylcarbonyl group or a lower alkylsulfonyl group, the loweralkyl group, lower alkoxy group, lower alkylthio group, lower alkylaminogroup, amide of a lower alkylamino group, lower alkylcarbonyl group orlower alkylsulfonyl group may have one or a plurality of substituentsselected from the group consisting of a halogen atom, a lower cycloalkylgroup, an aryl group, a heterocyclic group, a hydroxy group, an ester ofa hydroxy group, a lower alkoxy group, a lower alkoxy group substitutedwith at least a halogen atom, a lower cycloalkyloxy group, an aryloxygroup, a heterocyclic oxy group, a lower alkylthio group, a lowercycloalkylthio group, an arylthio group, a heterocyclic thio group, anamino group, a lower alkylamino group, a lower cycloalkylamino group, anarylamino group, a heterocyclic amino group, an amide of an amino group,an amide of a lower alkylamino group, an amide of a lowercycloalkylamino group, an amide of an arylamino group, an amide of aheterocyclic amino group, a lower alkylcarbonyl group, a lowercycloalkylcarbonyl group, an arylcarbonyl group, a heterocyclic carbonylgroup, a carboxy group, an ester of a carboxy group, an amide of acarboxy group, a lower alkylsulfonyl group, a lower cycloalkylsulfonylgroup, an arylsulfonyl group, a heterocyclic sulfonyl group, a sulfonicacid group, an ester of a sulfonic acid group, an amide of a sulfonicacid group, a nitro group and a cyano group; p represents an integer of0 to 3; in the case where p is 2 or 3, each R¹ may be the same ordifferent; q represents 0; R³ represents a hydrogen atom, a lower alkylgroup, a lower alkenyl group, a lower alkylcarbonyl group, a loweralkenylcarbonyl group or an arylcarbonyl group; in the case where R³ isa lower alkyl group, the lower alkyl group may have one or a pluralityof aryl groups as substituents; in the case where R³ is an arylcarbonylgroup, the arylcarbonyl group may have one or a plurality ofsubstituents selected from the group consisting of a halogen atom and alower alkyl group; R⁴ and R⁵ are the same or different and represent ahalogen atom, a lower alkyl group, a lower cycloalkyl group, aryl or aheterocyclic group; in the case where R⁴ or R⁵ is a lower alkyl group,the lower alkyl group may have one or a plurality of substituentsselected from the group consisting of a halogen atom, a hydroxy group,an ester of a hydroxy group, a lower alkoxy group, a lower alkoxy groupsubstituted with at least a halogen atom, a lower alkylthio group, anamino group, a lower alkylamino group, an amide of an amino group, anamide of a lower alkylamino group, a lower alkylcarbonyl group, acarboxy group, an ester of a carboxy group, an amide of a carboxy group,a nitro group and a cyano group; in the case where R⁴ or R⁵ is a lowercycloalkyl group, aryl or a heterocyclic group, the lower cycloalkylgroup, aryl or heterocyclic group may have one or a plurality ofsubstituents selected from the group consisting of a halogen atom, alower alkyl group, a lower alkyl group substituted with at least ahalogen atom, a hydroxy group, an ester of a hydroxy group, a loweralkoxy group, a lower alkoxy group substituted with at least a halogenatom, a lower alkylthio group, an amino group, a lower alkylamino group,an amide of an amino group, an amide of a lower alkylamino group, alower alkylcarbonyl group, a carboxy group, an ester of a carboxy group,an amide of a carboxy group, a lower alkylsulfonyl group, a nitro groupand a cyano group; R⁴ and R⁵ may be combined together to form a 3- to8-membered lower cycloalkane ring; R⁶ represents a hydrogen atom, alower alkyl group, a lower alkenyl group, a lower alkynyl group or alower cycloalkyl group; in the case where R⁶ is a lower alkyl group, alower alkenyl group, a lower alkynyl group or a lower cycloalkyl group,the lower alkyl group, lower alkenyl group, lower alkynyl group or lowercycloalkyl group may have one or a plurality of substituents selectedfrom the group consisting of a halogen atom and an aryl group; Arepresents a lower alkylene group; R⁷ represents OR⁸, NR⁸R⁹ or SR⁸; R⁸and R⁹ are the same or different and represent a hydrogen atom, a loweralkyl group, a lower alkenyl group, a lower alkynyl group, a lowercycloalkyl group, an aryl group, a heterocyclic group, a formyl group, alower alkylcarbonyl group, a lower alkenylcarbonyl group, a loweralkynylcarbonyl group, a lower cycloalkylcarbonyl group, an arylcarbonylgroup, a heterocyclic carbonyl group, a carboxy group, a loweralkoxycarbonyl group, a lower alkenyloxycarbonyl group, a loweralkynyloxycarbonyl group, a lower cycloalkyloxycarbonyl group, anaryloxycarbonyl group, a heterocyclic oxycarbonyl group, a loweralkylsulfonyl group, a lower alkenylsulfonyl group, a loweralkynylsulfonyl group, a lower cycloalkylsulfonyl group, an arylsulfonylgroup, a heterocyclic sulfonyl group, an aminocarbonyl group, a loweralkylaminocarbonyl group, a lower alkenylaminocarbonyl group, a loweralkynylaminocarbonyl group, a lower cycloalkylaminocarbonyl group, anarylaminocarbonyl group or a heterocyclic aminocarbonyl group; in thecase where R⁸ or R⁹ is a lower alkyl group, a lower alkenyl group, alower alkynyl group, a lower alkylcarbonyl group, a loweralkenylcarbonyl group, a lower alkynylcarbonyl group, a loweralkoxycarbonyl group, a lower alkenyloxycarbonyl group, a loweralkynyloxycarbonyl group, a lower alkylsulfonyl group, a loweralkenylsulfonyl group, a lower alkynylsulfonyl group, a loweralkylaminocarbonyl group, a lower alkenylaminocarbonyl group or a loweralkynylaminocarbonyl group, the lower alkyl group, lower alkenyl group,lower alkynyl group, lower alkylcarbonyl group, lower alkenylcarbonylgroup, lower alkynylcarbonyl group, lower alkoxycarbonyl group, loweralkenyloxycarbonyl group, lower alkynyloxycarbonyl group, loweralkylsulfonyl group, lower alkenylsulfonyl group, lower alkynylsulfonylgroup, lower alkylaminocarbonyl group, lower alkenylaminocarbonyl groupor lower alkynylaminocarbonyl group may have one or a plurality ofsubstituents selected from the group consisting of a halogen atom, alower cycloalkyl group, an aryl group, a heterocyclic group, a hydroxygroup, an ester of a hydroxy group, a lower alkoxy group, a lower alkoxygroup substituted with at least a halogen atom, a lower alkylthio group,an amino group, a lower alkylamino group, an amide of an amino group, anamide of a lower alkylamino group, a lower alkylcarbonyl group, acarboxy group, an ester of a carboxy group, an amide of a carboxy group,a lower alkylsulfonyl group, a nitro group and a cyano group; in thecase where R⁸ or R⁹ is a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower cycloalkylcarbonyl group, an arylcarbonylgroup, a heterocyclic carbonyl group, a lower cycloalkyloxycarbonylgroup, an aryloxycarbonyl group, a heterocyclic oxycarbonyl group, alower cycloalkylsulfonyl group, an arylsulfonyl group, a heterocyclicsulfonyl group, a lower cycloalkylaminocarbonyl group, anarylaminocarbonyl group or a heterocyclic aminocarbonyl group, the lowercycloalkyl group, aryl group, heterocyclic group, lowercycloalkylcarbonyl group, arylcarbonyl group, heterocyclic carbonylgroup, lower cycloalkyloxycarbonyl group, aryloxycarbonyl group,heterocyclic oxycarbonyl group, lower cycloalkylsulfonyl group,arylsulfonyl group, heterocyclic sulfonyl group, lowercycloalkylaminocarbonyl group, arylaminocarbonyl group or heterocyclicaminocarbonyl group may have one or a plurality of substituents selectedfrom the group consisting of a halogen atom, a lower alkyl group, alower alkyl group substituted with at least a halogen atom, a loweralkyl group substituted with at least a hydroxy group, a lower alkenylgroup, a lower alkynyl group, a lower cycloalkyl group, an aryl group, aheterocyclic group, a hydroxy group, an ester of a hydroxy group, alower alkoxy group, a lower alkoxy group substituted with at least ahalogen atom, a lower alkenyloxy group, a lower alkynyloxy group, alower alkylthio group, an amino group, a lower alkylamino group, anamide of an amino group, an amide of a lower alkylamino group, a loweralkylcarbonyl group, a carboxy group, an ester of a carboxy group, anamide of a carboxy group, a lower alkylsulfonyl group, a nitro group anda cyano group; in the case where R⁷ is NR⁸R⁹, R⁸ and R⁹ may be combinedtogether to form a 5- or 6-membered nitrogen-containing heterocyclicring; and X represents O.
 4. The compound or a salt thereof according toany one of claims 1 to 3, wherein in the formula (1), A represents amethylene group.
 5. A pharmaceutical composition, comprising atherapeutically effective amount of the compound or a salt thereofaccording to any one of claims 1 to 3 in combination with apharmaceutically acceptable carrier.
 6. A method of preventing ortreating a glucocorticoid receptor-related disease, comprisingadministering to a patient in need thereof a therapeutically effectiveamount of the compound or a salt thereof according to any one of claims1 to
 3. 7. The method according to claim 6, wherein the glucocorticoidreceptor-related disease is a metabolic disorder, an inflammatorydisease, an autoimmune disease, an allergic disease, a central nervoussystem disease, a cardiovascular disease, a homeostasis-related diseaseor glaucoma.